The aim — to determine the influence of the variability of home blood pressure (BP) on the effectiveness of algorithmic antihypertensive treatment in the initial stage in patients with uncomplicated arterial hypertension (AH) in clinical practice.
Materials and methods. The study involved 209 patients with uncomplicated essential AH aged 35 to 75 years including those who had not received treatment before (with BP ≥ 160/100 mm Hg) and those who had previously received antihypertensive therapy (with BP ≥ 140/90 mm Hg). Step by step treatment algorithm implied initial prescription of a fixed combination of perindopril and amlodipine and, if necessary, subsequent prescription of indapamide, spironolactone, moxonidine or doxazosin to achieve the target office blood pressure (< 140/90 mm Hg). BP was measured automatically using oscillometry instrument with a universal or individually selected cuff: office BP — during the first and each subsequent visit (in 7 days, and in 1, 2, 3, 6 months), home BP — twice a day (before breakfast and before bedtime for at least 7 consecutive days before the visit to the doctor). Variability of home blood pressure was measured by the standard deviation (SD), coefficient of variation (CV) of average BP value and the variation independent of mean (VIM).
Results and discussion. According to median of SD of average value of home systolic blood pressure (SBP) which equaled 8.5 mm Hg, the patients were divided into two groups: 104 people with SD ≥ 8.5 mm Hg (I group) and 105 people with SD < 8.5 mm Hg (II group). I group included a greater number of persons with an initial office heart rate (HR) of more than 75 per 1 min (p < 0.05) and a higher initial average HR (p < 0.03) but fewer smokers and more persons burdened with regard to cardiovascular disease heredity (p < 0.01) than II group. Patients of I group had higher average values of SD, CV and VIM of home SBP during the whole course of treatment, and SD and CV of diastolic BP (DBP) at baseline and in 1, 3 and 6 months than those of II group. Throughout the study period, the average home SBP and DBP in I group were lower than in II group. At the initial stage of the study, the average value of home BP in II group exceeded that in I group at comparable levels of pulse pressure. For the 6 months of treatment, the value of both of these indicators was significantly decreased in all patients, but during the 1st, 3rd and 6th months of the study, this value in I group remained smaller than in II group. The proportion of patients with the recommended level of home blood pressure in I group in 1 (54.8 and 39 %; p < 0.03), 3 (72.1 and 57.1 %; p < 0.03) and 6 (75 and 61 %; p < 0.05) months of treatment was significantly greater compared with that in II group.
Conclusions. High variability of home BP in patients with uncomplicated AH in 7 days after prescription of the fixed combination of perindopril and amlodipine is associated with a more pronounced decline in home BP, greater frequency of achievement of its recommended level and less frequently of masked uncontrolled hypertension in 6 months of stepwise algorithmic therapy. High variability of home BP in patients with uncomplicated AH in 7 days after administration of a fixed combination of perindopril and amlodipine, compared to its low level, is associated with a reduction in the frequency of masked uncontrolled hypertension among patients with target office BP during 6 months of stepwise algorithmic treatment. High variability of home BP in patients with uncomplicated AH in 7 days after administration of a fixed combination of perindopril and amlodipine, compared to its low level, is associated with a lower value of surrogate indices of vascular stiffness, namely, pulse and mean arterial pressure within 6 months of stepwise algorithmic treatment.

Keywords: arterial hypertension, blood pressure, home blood pressure, home blood pressure variability, fixed drug combination, perindopril, amlodipine.

Additional: Article received 20 Jun 2016

The aim — to investigate demographic, anamnestic, baseline clinical, laboratory and instrumental parameters and their dynamics during the hospital period in patients with acute ST-segment elevation myocardial infarction (STEMI) depending on the value of phenylalanine/tyrosine ratio in plasma of patients on the admission day.
Materials and methods. The study was based on prospective examination of 92 patients with acute STEMI (66.3 % — males; mean age — 59.2 ± 9.3 years) who were not treated by revascularization methods. All the patients were divided into two groups depending on the baseline value of phenylalanine/tyrosine ratio in plasma: I group included the patients with phenylalanine/tyrosine ratio in plasma ≤ 2.06 (n = 67) and II group — the patients with phenylalanine/tyrosine ratio in plasma > 2.06 (n = 25). The concentrations of plasma amino acids were analyzed by cation-exchanged liquid-column chromatography on the day of admission.
Results and discussion. The patients of II group more frequently suffered from stable angina pectoris (84.0 % vs 43.3 %, p = 0.001), previous myocardial infarction (28.0 % vs 5.97 %, p = 0.011), arterial hypertension (100.0 % vs 77.6 %, p = 0.023) and chronic heart failure (84.0 % vs 43.3 %, p = 0.001) in history. On the day of admission, acute left ventricular failure (LVF) (72.0 % vs 35.8 %, p = 0.002) and sinus tachycardia (48.0 % vs 25.4 %, p = 0.038) were diagnosed more often in II group than in I group. The baseline erythrocyte sedimentation rate was higher 17.3 ± 13.3 mm/h vs 10.9 ± 9.2 mm/h, p < 0.01) and glomerular filtration rate was lower 70.9 ± 34.1 ml/min vs 89.1 ± 30.3 ml/min, p < 0.05) in II group compared with I group. The dynamics of the laboratory parameters was statistically significant in the patients of both groups, but plasma level of globulins was significantly reduced on the tenth day (by 12.0 %, p < 0.01, compared with the baseline level) only in I group. Baseline systolic, diastolic and average blood pressure levels were higher in I group (by 18.2 %, p = 0.003; by 20.6 %, p = 0.00002, and by 19.5 %, p = 0.0002, respectively, compared with the II group) with significant decrease in these parameters during the ten days’ treatment period. There was no statistically significant difference between the groups in the baseline characteristics of electrocardiography, echocardiography and prevalence of early systolic dysfunction of left ventricle at the day of admission. However the improved value of wall motion score index of left ventricle during the ten days of hospital period was revealed only in I group. The complicated course of acute STEMI (96.0 % vs 61.2 %, p = 0.003), resistant/late left ventricular failure (on the third day of hospital period or later) (56.0 % vs 26.9 %, p = 0.009) and life-threatening arrhythmias (28.0 % vs 10.5 %, p = 0.037) were diagnosed more often in II group compared with I group.
Conclusions. The baseline phenylalanine/tyrosine ratio in plasma > 2.06 as an indirect marker of tetrahydrobiopterine deficiency and limited capacity of endogenous cardioprotection systems is revealed in 27 % of patients with acute STEMI and is associated with more frequent development of acute left ventricular failure, laboratory inflammation syndrome and lack of hypertensive reactions on the day of admission. In case of equal baseline localization of STEMI, size of ischemic injury, systolic and diastolic parameters of left ventricle and the same treatment, the patients with baseline phenylalanine/tyrosine ratio in plasma > 2.06 are characterized by much worse prognosis for uncomplicated hospital course of STEMI and recovery of regional contractility of left ventricle compared to the patients with phenylalanine/tyrosine ratio in plasma ≤ 2.06.

Keywords: acute ST-segment elevation myocardial infarction, cardioprotection, plasma amino acids, phenylalanine/tyrosine ratio.

Additional: Article received on 16 June 2016

The aim — to assess the fractalkine and asymmetrical dimethylarginine (ADMA) levels in patients with coronary artery disease (CAD), depending on the presence of type 2 diabetes mellitus (T2DM), and the nature of coronary artery lesions, as also their importance in predicting the presence and severity of coronary atherosclerotic lesions.
Materials and methods. 131 patients with CAD (89 men, 42 women, mean age of (59.6 ± 9.11) years) were examined. Depending on the presence of T2DM, patients with CAD were divided into 2 groups: I group (n = 70) — patients with concomitant T2DM, II group (n = 61) — patients without concomitant T2DM. All patients underwent coronary angiography to verify the diagnosis of coronary artery disease. Also the levels of fractalkine and ADMA were assessed.
Results and discussion. The study demonstrated that CAD patients, both with concomitant T2DM and without it, had significantly increased levels of fractalkine and ADMA compared with the control group (p < 0.05). Patients with hemodynamically significant stenosis of coronary arteries had significantly elevated levels of fractalkine (p < 0.05). At the same time, ADMA levels were not significantly different between subgroups based on the presence of hemodynamically significant stenosis of the coronary arteries (p > 0.05). Patients with diffuse CAD with and without T2DM had significantly higher fractalkine levels than patients without diffuse coronary artery lesions (p < 0.05). Patients with CAD associated with T2DM and diffuse coronary artery lesions, had significantly increased ADMA levels compared to patients without diffuse lesions of coronary vessels (p < 0.05). Patients with CAD without concomitant T2DM had nonsignificant trend to elevation of ADMA level in diffuse lesions of coronary vessels (p > 0.05). When comparing the areas under ROC-curves of fractalkine and ADMA levels for predicting the presence of atherosclerotic lesions of coronary vessels it has been found that ADMA levels have significant diagnostic value. Fractalkine level had greater diagnostic value for predicting the presence of diffuse coronary vessel lesions.
Conclusions. Determination of fractalkine and ADMA levels is important in predicting the presence of atherosclerotic lesions of coronary vessels and in diagnosing hemodynamically significant coronary artery stenosis and diffuse coronary lesions.

Keywords: fractalkine, asymmetrical dimethylarginine, atherosclerosis of coronary vessels, type 2 diabetes mellitus.

Additional: Article received 20 Jun 2016

The aim — to estimate the functional state of the vascular endothelium, the elastic properties of the main arteries and the morphofunctional status of the heart in patients with essential hypertension (EH) complicated with chronic heart failure (CHF) with preserved ejection fraction (EF) of the left ventricle (LV).
Materials and methods. 120 hypertensive patients aged 67.8 ± 1.2 yrs (30 EH patients without CHF and 90 EH patients with CHF and preserved LV EF) were examined by 6-minute walk test, Doppler echocardiography, endothelium-dependent vasodilatation (EDVD). Central haemodynamics and elastic properties of the aorta were investigated by oscillometry.
Results and discussion. EDVD degree was 3 times higher in HP without CHF than in HP with CHF and preserved LV EF (7.4 ± 1.1 % vs. 2.3 ± 0.6 %, respectively). Endothelial dysfunction was registered in 100 % of CHF cases and only in 40 % of isolated HP cases. Insufficient EDVD was a prevailed type of endothelial dysfunction in CHF and preserved LV EF (71 %). The insufficient EDVD was associated with quality of life deterioration according to Minnesota questionnaire (r = –0.4; p < 0.01) and shortening of 6-minute walk distance (r = 0.37; р < 0.01). 2-fold increase of ultrasound local aortic stiffness and accelaration by 37 % of pulse wave velocity (PWV) was noticed in CHF and preserved LV EF compared to the control group (p < 0.02). There was parallelism between aorta elasticity (AE) decrease and endothelial dysfunction (EDVD) (r = –0.2; p < 0.05). The intima-media thickening characteristic for CHF with preserved LV EF is considered as essential mechanism of worsening aorta elastic properties. Against the background of a more pronounced left ventricular hypertrophy (LVH) in CHF (myocardial mass index (MMI) 133 ± 3 vs 115 ± 6 g/m2) and increased left atrial size 3.85 ± 0.05 vs 3.67 ± 0.07 cm) there was a negative correlation between EDVD and MMI (r = –0.25; p < 0.05).
Conclusions. Еndothelial dysfunction, found in 100 % cases of CHF with preserved LV EF, was associated with increased rigidity of the elastic arteries, an increasing degree of LVH and diastolic function deterioration.

Keywords: endothelial function, arterial stiffness, pulse wave velocity, elderly age.

List of references:  
1.    Voronkov LGh, Amosova KM, Baghrij AE, Dzjak Gh. V., Djadyk OI, Zharinov OJ, Kovalenko VM, Korkushko OV, Nesukaj OGh, Rudyk JuS, Parkhomenko OM. Rekomendaciji Asociaciji kardiologhiv Ukrajiny ta Ukrajinsjkoji asociaciji fakhivciv iz sercevoji nedostatnosti z diaghnostyky ta likuvannja khronichnoji sercevoji nedostatnosti [The recommendations of the Association of cardiologists of Ukraine and the Ukrainian Association of specialists in heart failure diagnosis and treatment of chronic heart failure]. Ukrainskyi kardiolohichnyi zhurnal. 2014; suppl. 1:6-8. (Ukrainian).
2.    Shishkin AN, Lyndina ML. Endotelialnaya disfunktsiya i arterialnaya gipertenziya [Endothelial dysfunction and arterial hypertension]. Arterialnaya gipertenziya. 2008;14(4):315-319. (Russian).
3.    Ageenkova OA, Purygina MA. Central aortic blood pressure, augmentation index, and reflected wave transit time: reproducibility and repeatability of data obtained by oscillometry. Vascular Health and Risk Management. 2011;7:649-656. (Russian).
4.    Bell V, Mitchell GF. [abstract]. Influence of vascular function and pulsatile hemodynamics on cardiac function. Curr Hypertens Rep. 2015;17(9):580.
5.    Bell V, Sigurdsson S, Westenberg JJ et al. Relations between aortic stiffness and left ventricular structure and function in older participants in the Age, Gene/Environment Susceptibility-Reykjavik Study. Circ Cardiovasc Imaging. 2015;8, N 4. e003039. doi: 10.1161/CIRCIMAGING.114.003039.
6.    Celermajer DS, Sorensen KE, Gooch VM et al. Non-invasive detection of mediated brachial artery vasodilatation in human subjects. Circulat Res. 1992;340:1111-1115.
7.    Faber M, Moller-Hou G. The human aorta. Part V. Collagen and elastin in the normal and hypertensive aorta. Acta Pathol Microbiol Scand. 1952;31:377-382.
8.    Flammer AJ, Anderson T, Celermajer DS et al. The Assessment of Endothelial Function — From Research into Clinical Practice. Circulation. 2012;126(6):753-767.
9.    Giamouzis G, Schelbert EB, Butler J. Growing Evidence Linking Microvascular Dysfunction With Heart Failure With Preserved Ejection Fraction. J Am Heart Assoc. 2016;5, N 2. e003259. doi: 10.1161/JAHA.116.003259.
10.    Harris RA, Nishiyama SK, Wray DW et al. Ultrasound Assessment of Flow-Mediated Dilation. Hypertension. 2010;55:1075-1085.
11.    Harvey A, Montezano AC, Lopes RA et al. Vascular Fibrosis in Aging and Hypertension: Molecular Mechanisms and Clinical Implications. Can J Cardiol. 2016;32(5):659-668.
12.    Mackenzie IS, Wilkinson IB, Cockcroft JR. Assessment of arterial stiffness in clinical practice. QJM: An International Journal of Medicine. 2002;95(2):67-74.
13.    Marti CN, Gheorghiade M, Kalogeropoulos AP et al. Endothelial dysfunction,arterial stiffness, and heart failure. J Am Coll Cardiol. 2012;60(16):1455-1469.
14.    Munakata M, Nunokawa T, Ito N et al. Clinical usefulness of novel measurement device for pulse wave velocity in human [abstract]. J Hypertens. 2001;19(2):23.
15.    Ruggiero D. Paolillo S, Ratta GD et al. Endothelial function as a marker of pre-clinical atherosclerosis: assessment techniques and clinical implications. Monaldi Arch Chest Dis. 2013;80(3):106-110.
16.    Thijssen DH, Black MA, Pyke KE et al. Assessment of flow-mediated dilation in humans: a methodological and physiological guideline. Am J Physiol Heart Circ Physiol. 2011;300(1):2-12.
17.    Tschöpe C, Van Linthout S. New insights in (inter)cellular mechanisms by heart failure with preserved ejection fraction. Curr Heart Fail Rep. 2014;11(4):436-444.
18.    Yamashina A, Tomiyama H, Takeda K. Validity, reproducibility and clinical significance brachial-ankle pulse wave velocity measurement. Hypertens Res. 2002;25(3):359-364.

Additional: Article received 17 Jun 2016

The aim — to investigate long-term survival of patients with polyarteritis nodosa (PAN) and antineutrophil cytoplasmic antibody associated vasculitis (ANCA-associated vasculitis) and to determine predictors of poor survival.
Materials and methods. The study included 53 patients with PAN and 49 patients with ANCA-associated vasculitis (granulomatosis with polyangiitis (GPA) — 27 persons, microscopic polyangiitis (MPA) — 10 persons, eosinophilic granulomatosis with polyangiitis — 12 persons). Among patients with PAN were 19 (35.8 %) women and 34 (64.2 %) men, average age — 41.5 years. Among patients with ANCA-associated vasculitis there were 34 women (69.4 %) and 15 men (30.6 %), average age — 48.5 years. The median duration of follow-up was 92 months for PAN and 62 months for ANCA-associated vasculites. Survival was evaluated as a function of the main demographics, clinical and laboratory parameters and Birmingham Vasculitis Activity Score (BVAS). Statistical analyses used the Kaplan — Meier method to determine the cumulative survival and generalized Wilcoxon — Gehana criteria to compare survival in groups. Predictors of poor survival of patients were determined using regression analysis by creation of Cox’s proportional intensities model.
Results and discussion. During the observation period, 15 patients with PAN (28.3 %) and 6 patients with ANCA-associated vasculitis (12.2 %) — 4 MPA patients and 2 patients with GPA died. The main causes of death of patients with primary systemic vasculites were multiple organ failure due to disease activity (47.6 %), renal failure (23.8 %) and infectious complications (28.6 %). According to the analysis, 25 % of patients with PAN die within the first 7 years, and 50 % of patients with PAN do not live more than 17 years. The survival rates of patients with PAN and ANCA-associated vasculites at the 1st, 3rd, 5th and 10th years of follow-up were 88.6 %, 84.2 %, 81.8 %, 68.2 % and 91.8 %, 87.6 %, 87.6 %, 76.7 %, respectively. Gender cumulative survival functions of patients with different primary systemic vasculites probably were no different, and in patients with PAN, the age at onset of the disease more than 60 years reduces survival. The presence of increased creatinine over 140 mkmol/l, myocarditis and age of patients over 60 years are poor prognostic factors in patients with PAN and increased serum creatinine over 176 mkmol/l and the presence of hemorrhagic alveolitis — in patients with ANCA-associated vasculites.
Conclusions. Despite standard treatment, the prognosis for patients with primary systemic vasculites remains unfavorable: the cumulative survival of patients with PAN during the first ten years decreased from 89 % (1st-year) to 68 %, which is lower compared to patients with ANCA-associated vasculites — from 92 % (1st-year) to 77 %. Predictors of poor survival rate of patients with PAN are increased creatinine over 140 mkmol/l, the presence of myocarditis and age of patients over 60 years and in patients with ANCA-associated vasculitis — increased serum creatinine over 176 mkmol/l and the presence of hemorrhagic alveolitis. Determination of poor prognostic factors may be important for intensifying induction therapy schemes.

Keywords: primary systemic vasculitis, ANCA-associated vasculitis, polyarteritis nodosa, survival.

List of references:  
1.    Khalafian АА. Statistica 6. Statystychnyi analyz danykh: pidruchnyk. [Statistica 6. Statistical analysis of data: a textbook.]. Moscow; 2008:512. (Russian).
2.    Aasarod K, Iversen B, Hammerstrom J et al. Wegener’s granulomatosis: clinical course in 108 patients with renal involvement. Nephrol Dial Transplant. 2000;15:611-618.
3.    Flossmann O, Berden A, de Groot K et al. Long-term patient survival in ANCA-associated vasculitis. Ann Rheum Dis. 2011;70(3):488-494.
4.    Guillevin L, Dörner T. Vasculitis: mechanisms involved and clinical manifestations. Arthritis Res Ther. 2007;9(2):9.
5.    Guillevin L, Lhote F, Gayraud M et al. Prognostic factors in polyarteritis nodosa and Churg-Strauss syndrome. A prospective study in 342 patients. Medicine Baltimore. 1996;75:17-28.
6.    Guillevin L, Pagnoux C, Seror R et al. The Five-Factor Score revisited: assessment of prognoses of systemic necrotizing vasculitides based on the French Vasculitis Study Group (FVSG) cohort. Medicine (Baltimore). 2011;90(1):19-27.
7.    Harper L, Savage C. ANCA-associated renal vasculitis at the end of the twentieth century — a disease of older patients. Rheumatology. 2005;44:495-501.
8.    Hogan S, Falk R, Chin H et al. Predictors of relapse and treatment resistance in antineutrophil cytoplasmic antibody-associated small-vessel vasculitis. Ann Intern Med. 2005;143:621-631.
9.    Holle J. Gross W, Latza U et al. Improved outcome in 445 patients with Wegener’s granulomatosis in a German vasculitis center over four decades. Arthritis Rheum. 2011;63:257-266.
10.    Jennette J. Overview of the 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Clin Exp Nephrol. 2013;7(5):603-606.
11.    Jennette J, Falk R, Andrassy K et al. Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis Rheum. 1994;37:187-192.
12.    Lightfoot R, Michel В, Bloch D et al. The American College of Rheumatology 1990 criteria for the classification of polyarteritis nodosa. Arthritis Rheum. 1990;33:88-93.
13.    Mukhtyar C, Guillevin L, Cid M et al. EULAR recommendations for the management of primary small and medium vessel vasculitis. Ann Rheum Dis. 2009;68(3):310-327.
14.    Mukhtyar C, Lee R, Brown D et al. Modification and validation of the Birmingham vasculitis activity score (Version 3). Ann Rheum Dis. 2009;68:1827-1832.
15.    Pagnoux C, Seror R, Henegar C et al. Clinical features and outcomes in 348 patients with polyarteritis nodosa: a systematic retrospective study of patients diagnosed between 1963 and 2005 and entered into the French Vasculitis Study Group Database. Arthritis Rheum. 2010;62:616-626.
16.    Phillip R, Luqmani R. Mortality in systemic vasculitis: a systematic review. Clin Exp Rheumatol. 2008;26(5):94-104.
17.    Slot M, Tervaert J, Franssen C et al. Renal survival and prognostic factors in patients with PR3-ANCA associated vasculitis with renal involvement. Kidney Int. 2003;63:670-677.
18.    Watts RA. Vasculitis in Clinical. Practice Oxford University Press, 2008:4-5.
19.    Weidner S, Geuss S, Hafezi-Rachti S et al. ANCA-associated vasculitis with renal involvement: an outcome analysis. Nephrol Dial Transplant. 2004;19:1403-1411.
20.    Westman K, Bygren P, Olsson H et al. Relapse rate, renal survival, and cancer morbidity in patients with Wegener’s granulomatosis or microscopic polyangiitis with renal involvement. J Am Soc Nephrol. 1998;9:842-852.
21.    Westman K, Flossmann O, Gregorini G. The long-term outcomes of systemic vasculitis. Nephrol Dial Transplant. 2015;30(1):60-66.
22.    Westman K, Selga D, Isberg P et al. High proteinase 3-anti-neutrophil cytoplasmic antibody (ANCA) level measured by the capture enzyme-linked immunosorbent assay method is associated with decreased patient survival in ANCA-associated vasculitis with renal involvement. J Am Soc Nephrol. 2003;14:2926-2933.

Additional: Article received 17 Jun 2016

The aim — to study the relationship between chemerin and nesfatin-1 serum levels and features of ambulatory blood pressure monitoring (ABPM) in patients with essential hypertension (EH), depending on the body mass index (BMI).
Materials and methods. ABPM was conducted in 82 hypertensive patients aged 60 (55; 66) years (including 26 patients with overweight and 39 with obesity). Serum levels of chemerin and nesfatin-1 were determined by ELISA using Human Chemerin and Human Nesfatin-1 ELISA kits (Kono Biotech Co., Ltd., China). Statistical analysis was performed using the Mann-Whitney test, Pearson criterion, cluster analysis. Quantitative characteristics were presented as median, upper and lower quartiles.
Results and discussion. Serum levels of chemerin and nesfatin-1 were significantly higher in patients with hypertension (p = 0.001) compared with healthy individuals, regardless of BMI. To identify the impact of both cytokines’ concentration on ABPM parameters, cluster analysis by the method of k-means was performed, obtaining four clusters with an accuracy of p = 0.138. Inter-cluster analysis has revealed the statistically significant differences between the parameters of ABPM that characterize the dynamics in the morning blood pressure change, such as speed (SMISBP and SMIDBP) and quantity (TMISBP and TMIDBP) of morning increase in blood pressure, daytime systolic and diastolic blood pressure variability (VarSBP (D) and VarDBP (D)), and circadian rhythm of blood pressure. The 1st cluster (where high levels of serum chemerin — 11.12 (8.2; 14.02) ng/mL — were associated with high values of BMI — 33.31 (30.47; 36.15) kg/m2) appeared to be the most prognostically unfavorable according to the type of circadian patterns of blood pressure distribution, values of VarSBP and VarDBP. In contrast, patients of the third cluster with high levels of both cytokines in the serum (chemerin — 7.7 (6.52; 8.44) ng/ml, nesfatin-1 — 8.96 (8.55; 9.37) ng/ml and a low BMI (25.2 (23.1; 26.8) kg/m2) had a prevailing «dipper» type distribution of circadian rhythm of blood pressure, but high SMISBP and SMIDBP. The 2nd cluster with moderately low chemerin — 4.91 (4.42; 5.26) ng/ml, and high nesfatin-1 levels — 8.02 (7.67, 8.43) ng/ml turned out to be the most favorable in relation to the ABPM indices. The correlation analysis has revealed the presence of moderate direct correlation between the serum chemerin and the following parameters of ABPM: SMISBP and SMIDBP (r = 0.35, p < 0.05); TMISBP and TMIDBP (r = 0.3, p < 0.05); VarSBP and VarDBP (r = 0.34, p < 0.05). There was no correlation revealed between the parameters of ABPM and nesfatin-1 serum levels.
Conclusions. Serum levels of chemerin and nesfatin-1 in patients with essential hypertension were significantly increased compared to the control group, regardless of the presence and degree of obesity. The study has shown the association between serum levels of chemerin and circadian rhythm, daily variability of blood pressure and ABPM parameters characterizing the dynamics of morning blood pressure change. The compelling evidence of the nesfatin-1 levels impact on the indices of ABPM has not been found.

Keywords: essential hypertension, obesity, ambulatory blood pressure monitoring, cytokines, chemerin, nesfatin-1.

Additional: Article received 22 June 2016

The article highlights the modern scientific literature data on the research of microRNA-126. Particular attention is paid to the impact of microRNA-126 on the pathological and physiological angiogenesis, ways of its use in the diagnostics (as a marker of activation of angiogenesis) and in the treatment of ischemic limbs diseases. The article shows the prospects of microRNA-126 use in vascular surgery, cardiology, onсology.

Keywords: microRNA, angiogenesis, polymerase chain reaction, SPRED 1 protein, vascular endothelial growth factor.

List of references:  
1.    Appel B. Nukleinovyie kislotyi: ot A do Ya. — M.: Binom: Laboratoriya znaniy (Russian). 2013:413.
2.    Galitskiy VA. Gipoteza o mehanizme initsiatsii malyimi RNK metilirovaniya DNK de novo i allelnogo isklyucheniya. Tsitologiya (Russian). 2008;50 (4):277-286.
3.    Anand S, Cheresh DA. Emerging. Role of Micro-RNAs in the Regulation of Angiogenesis. Genes Cancer. 2011;2(12):1134-1138.
4.    Buermans HP, Ariyurek Y, van Ommen G et al. New methods for next generation sequencing based microRNA expression profiling. BMC Genomics. 2009:711-716. DOI:10.1186/1471-2164-11- 716.
5.    Chen C, Ridzon DA, Broomer AJ et al. Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res. 2005;33 (20):179. DOI:10.1093/nar/gni178. PMID 16314309.
6.    Feng J, Sun G, Yan J et al. Evidence for X-chromosomal schizophrenia associated with microRNA alterations. Sommer SS. 2009:54.
7.    Finch ML, Marquardt JU, Yeoh GC, Callus BA. Regulation of microRNAs and their role in liver development, regeneration and disease. Int J Biochem Cell Biol. 2014;DOI: 10.1016/j.biocel.2014.04.002. PMID 24731940.
8.    Friedländer MR, Lizano E, Houben AJ et al. Evidence for the biogenesis of more than 1,000 novel human microRNAs. Genome Biol. 2014;15(4):57.
9.    Gregory PA, Bert AG, Paterson EL et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol. 2011;10 (5):593-601. DOI:10.1038/ncb1722. PMID 18376396.
10.    He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nature. 2006;5 (7):522-531. DOI: 10.1038/nrg1379. PMID 15211354.
11.    Hughes AE, Bradley DT, Campbell M et al. Mutation Altering the miR-184 Seed Region Causes Familial Keratoconus with Cataract. Am J Human Gen. 2011;89 (5):628-633. DOI: 10.1016/j.ajhg.2011.09.014.
12.    Insull W. The Pathology of Atherosclerosis: Plaque Development and Plaque Responses to Medical Treatment. Am J Med. 2009;122. P. S3—S14.
13.    Jansen F et al. Endothelial Microparticle — Mediated Transfer of MicroRNA-126 Promotes Vascular Endothelial Cell Repair via SPRED1 and Is Abrogated in Glucose-Damaged Endothelial Microparticles. Circulation— 2013— Vol 128 (18):12-14.
14.    Kusenda B, Mraz M, Mayer J, Pospisilova S. MicroRNA biogenesis, functionality and cancer relevance. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 150 (2):205-215. DOI: 10.5507/bp.2006.029. PMID 17426780.
15.    Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 120 (1):15-20. DOI: 10.1016/j.cell.2004.12.035.
16.    Møller HG, Rasmussen AP, Andersen HH et al. A Systematic Review of MicroRNA in Glioblastoma Multiforme: Micro-modulators in the Mesenchymal Mode of Migration and Invasion. Mol Neurobiol. 2013;47(1):131—144. DOI: 10.1007/s12035-012-8349-7.
17.    Morozova N, Zinovyev A, Nonne N et al. Kinetic signatures of microRNA modes of action. RNA. 2014;18 (9):1635- 1655. DOI: 10.1261/rna.032284.112. PMID 22850425.
18.    Peterson SM, Thompson JA, Ufkin ML et al. Common features of microRNA target prediction tools. Front Genet. 2014;5:23. DOI: 10.3389/fgene.2014.00023. PMID 24600468
19.    Rivas DA et al. Diminished skeletal muscle microRNA expression with aging is associated with attenuated muscle plasticity and inhibition of IGF-1 signaling. Faseb J. 2014;28 (9):4133-4147. DOI: 10.1096/fj.14-254490.
20.    Rodriguez A, Griffiths-Jones S, Ashurst JL, Bradley A. Identification of mammalian microRNA host genes and transcription units. Genome Res. 14 (10A):1902-1910. DOI: 10.1101/gr.2722704. PMID 15364901.
21.    Shingara J, Keiger K, Shelton J et al. An optimized isolation and labeling platform for accurate microRNA expression profiling. RNA. 2008;11 (9):1461-7150. DOI: 10.1261/rna.2610405. PMID 16043497.
22.    Tanzer A, Stadler PF. Molecular evolution of a microRNA cluster. J Mol Biol. 339 (2):327-235. DOI: 10.1016/j.jmb.2004.03.065. PMID 15136036.
23.    Tomasetti M et al. MicroRNA in Metabolic Re-Programming and Their Role in Tumorigenesis. HHS Public Access. 2016:46.
24.    Wei Y, Schober A, Weber C. Pathogenic arterial remodeling: the good and bad of microRNA. Am J Physiol Heart Circ Physiol. 2013;74:1050-1059. DOI: 10.1152/ajpheart.00267.2012.
25.    Zuo J et al. MicroRNA Transcriptome Profile Analysis in Porcine Muscle and the Effect of miR-143 on the MYH7 Gene and Protein. PLoS One. 2015;10 (4):1-21. DOI: 10.1371/journal.pone.0124873.

Additional: Article received 20 Jun 2016

The pathology of the cardiovascular system currently remains a major cause of disability and mortality around the world. Despite the in-depth study of the pathogenesis of cardiovascular disease (CVD), the incidence and mortality from this disease continues to grow steadily. Data of one of the largest studies — MONICA (Multinational Monitoring of Trends and Determinants in Cardiovascular Disease) — have shown that the presence of classical factors of atherogenesis risk (smoking, high systolic blood pressure, obesity and hypercholesterolemia) cannot fully explain the development of CVD, as their prevalence reaches 15 % in females and 40 % in males. In this regard, the search continues for new risk factors, reduction of which may decrease CVD mortality. Timely detection of risk factors for atherosclerosis and thrombosis, assessment of their impact on the course of the disease and adequate pathophysiological therapy open the way to improvement of this situation. Traditional ideas about the causes of the development of thrombosis and atherosclerosis have yet to reveal the mechanism of the real relationship of these diseases, which could help to carry out the prophylaxis and treatment of the two complex processes in blood vessels. The solution to this problem is possible if we consider both pathologies from perspective of equal significance of violation of their metabolic processes. The substance that has both atherogenic and thrombotic action is homocysteine (HC). Hyperhomocysteinemia (HHC) can be considered as an important independent modifiable cardiovascular risk factor of CVD, along with hypercholesterolemia and other risk factors such as smoking, diabetes, hypertension, obesity and others, as also a factor that increases the risk of developing cardiovascular disease in the presence of the above factors the patient. To date the determination of blood levels of HC is a priority method in the clinical diagnosis of CVD worldwide. The diagnosing of HHC should be carried out by the screening method in healthy people to identify high-risk of cardiovascular disease and take preventive measures against its reduction. Since HC is one of the factors for atherothrombotic process, people diagnosed with CVD and the HHC must be attributed to the group of persons at high risk for CVD. Thus an active tactics is necessary regarding the normalization and stabilization of the HC in the blood, which may reduce mortality and probably increase fertility in the country.

Keywords: cardiovascular disease, homocysteine, hyperhomocysteinemia, atherosclerosis, thrombosis.

List of references:  
1.    Arnadottir M, Hultberg B. Homocysteine in renal disease. Homocysteine in health and disease. Cambridge University Press, Cambridge, UK, 2001:321-330.
2.    Brattstrom L, Israelsson B, Olsson A et al. Plasma homocysteine in women on oral oestrogen-containing contraceptives and in men with oestrogen-treated prostatic carcinoma. Scand J Clin Lab Investig. 52:283-287.
3.    Brattstrom L, Landgren F, Israelsson B et al. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. Br Med J. 1998;316:894-898.
4.    Brouwer IA, Verhoef P, Urgert R. Betaine supplementation and plasma homocysteine in healthy volunteers. Arch Intern Med. 2000;160:2546-2547.
5.    Brown AA, Hu FB. Dietary modulation of endothelial function: implications for cardiovascular disease. Am J Clin Nutr. 2001;73:673-686.
6.    Chen J, Giovannucci EL, Hunter DJ. MTHFR polymorphism, methyl-replete diets and the risk of colorectal carcinoma and adenoma among U. S. men and women: an example of gene-environment interactions in colorectal tumorigenesis. J Nutr. 1999;129:560S-564S.
7.    Clarke R, Armitage J. Vitamin supplements and cardiovascular risk: review of the randomized trials of homocysteine-lowering vitamin supplements. Semin Thromb Hemost. 2002;26:341-348.
8.    Clarke R, Bennett DA, Parish S et al. Homocysteine and Coronary Heart Disease: Meta-analysis of MTHFR Case-Control Studies, Avoiding Publication Bias. PLoS Med. 2012;9 (2). P. e1001177.
9.    Clarke R, Collins R. Can dietary supplements with folic acid or vitamin B6 reduce cardiovascular risk? Design of clinical trials to test the homocysteine hypothesis of vascular disease. J Cardiovasc Risk. 1998;5:249-255.
10.    Dallongeville J, Marecaux N, Fruchart JC, Amouyel P. Cigarette smoking is associated with unhealthy patterns of nutrient intake: a meta-analysis. J Nutr. 1998;128:1450-1457.
11.    De Jong SC, Stehouwer CD, van den B. M. et al. Normohomocysteinaemia and vitamintreated hyperhomocysteinaemia are associated with similar risks of cardiovascular events in patients with premature peripheral arterial occlusive disease. A prospective cohort study. J Intern Med. 1999;246:87-96.
12.    De Vriese AS, Verbeke F, Schrijvers BF, Lameire NH. Is folate a promising agent in the prevention and treatment of cardiovascular disease in patients with renal failure? Kidney Int. 2002;61:1199-1209.
13.    Ermens AA, Refsum H, Rupreht J et al. Monitoring cobalamin inactivation during nitrous oxide anesthesia by determination of homocysteine and folate in plasma and urine. Clin Pharmacol Ther. 1991;49:385-393.
14.    Ganguly P, Alam  S.F. Role of homocysteine in the development of cardiovascular disease. Nutrition J. 2015;14 (1).
15.    Giltay EJ, Hoogeveen EK, Elbers JM et al. Effects of sex steroids on plasma total homocysteine levels: a study in transsexual males and females. J Clin Endocrinol Metab. 1998;83:550-553.
16.    Grubben MJ, Boers GH, Blom HJ et al. Unfiltered coffee increases plasma homocysteine concentrations in healthy volunteers: a randomized trial. Am J Clin Nutr. 2000;71:480-484.
17.    Hackam DG, Peterson JC, Spence JD. What level of plasma homocyst(e)ine should be treated? Effects of vitamin therapy on progression of carotid atherosclerosis in patients with homocyst(e)ine levels above and below 14 micromol/L. Am J Hypertens. 2000;13:105-110.
18.    Konings EJ. M. Dietary folates in human nutrition.— Maastricht: University of Maastricht, 2001:151.
19.    Norlund L, Grubb A, Fex G et al. The increase of plasma homocysteine concentrations with age is partly due to the deterioration of renal function as determined by plasma cystatin C. Clin Chem Lab Med. 1998;36:175-178.
20.    Nygard O, Refsum H, Ueland PM et al. Coffee consumption and plasma total homocysteine: the Hordaland Homocysteine study. Am J Clin Nutr. 1997;65:136-143.
21.    Refsum H, Ueland PM. Clinical significance of pharmacological modulation of homocysteine metabolism. Trends Pharmacol Sci. 1990;11:411-416.
22.    Schneede J, Refsum H, Ueland PM. Biological and environmental determinants of plasma homocysteine. Semin Thromb Hemost. 2000;26:263-279.
23.    Schnyder G, Roffi M, Pin R et al. Decreased rate of coronary restenosis after lowering of plasma homocysteine levels. N Engl J Med. 2001;345:1593-1600.
24.    Schwaninger M, Ringleb P, Winter R et al. Elevated plasma concentrations of homocysteine in antiepileptic drug treatment. Epilepsia. 1999;40:345-350.
25.    Stamler JS, Osborne JA, Jaraki O et al. Adverse vascular effects of homocysteine are modulated by endothelium-derived relaxing factor and related oxides of nitrogen. J Clin Invest. 1993;91:308 —318.
26.    Starkebaum G, Harlan J. M: Endothelial cell injury due to copper-catalyzed hydrogen peroxide generation from homocysteine. J Clin Invest. 1986;77:1370 —1376.
27.    Ubbink JB, van der M. A., Delport R et al. The effect of a subnormal vitamin B-6 status on homocysteine metabolism. J Clin Investig. 1996;98:177-184.
28.    Ueland PM, Refsum H. Plasma homocysteine, a risk factor for vascular disease: plasma levels in health, disease and drug therapy. J Lab Clin Med. 1989;114:473-501.
29.    Verhaar MC, Wever RM, Kastelein JJ et al. 5-methyltetrahydrofolate, the active form of folic acid, restores endothelial function in familial hypercholesterolemia. Circulation. 1998;97:237-241.
30.    Verhaar MC, Wever RM, Kastelein JJ et al. Effects of oral folic acid supplementation on endothelial function in familial hypercholesterolemia. A randomized placebocontrolled trial. Circulation. 1999;100:335-338.
31.    Vermeulen EG, Rauwerda JA, Erix P et al. Normohomocysteinaemia and vitamintreated hyperhomocysteinaemia are associated with similar risks of cardiovascular events in patients with premature atherothrombotic cerebrovascular disease. A prospective cohort study Neth J Med. 2000;56:138-146.
32.    Vermeulen EG.J., Stehouwer CD.A., Twisk JW.R. et al. Effect of homocysteine-lowering treatment with folic acid plus vitamin B-6 on progression of subclinical atherosclerosis: a randomised, placebo-controlled trial. Lancet. 2000;355:517-522.

Additional: Article received 21 Jun 2016

Review of the literature on the development of reperfusion syndrome was conducted to determine the pathophysiological changes in ischemic tissues of lower extremities after revascularization. It is proved that restoration of arterial blood flow is accompanied by damage and primary dysfunction of ischemic tissues and manifests itself as violation of the integrity of cell membranes, activation of apoptosis and necrosis of cells resulting from damage of power and ion exchange and increasing production of toxic oxygen species. There appears an oxidative stress, rapid decline in the energy potential of cells, violation of ion hemostasis accompanied by further imbalance of the antioxidant system and the progression of ischemia. The basic principles of diagnosis, prevention and treatment of reperfusion syndrome have been determined.

Keywords: reperfusion syndrome, revascularization of the lower extremities, pathophysiological changes.

List of references:  
1.    Horobets’ N.M. New Strategic Approaches Towards Correction of Endothelial Dysfunction (Ukrainian)/ Liky Ukrayiny (Ukrainian). 2015;2 (188):20-24.
2.    Kalinin RE, Pshennikov AS, Suchkov IA. Molecular mechanisms  of cellular protection in reconstructive-regenerative surgery of the main arterie. (Russian). Tihookeanskij medcinskij zhurnal (Russian). 2014;3 (57):52-55.
3.    Kalinin RE, Pshennikov AS, Suchkov IA. Realization of Ischemia and Reperfusion in Surgery of Major Arteries of the Lower Limbs (Russian). Novosti hirurgii (Russian). 2015;3 (23):51-56.
4.    Kalinin RE, Pshennikov AS, Suchkov IA. Reperfusion Injury of Tissues in Lower Limb Arterial Reconstructive Surgery (Russian). Novosti hirurgii (Russian). 2015;3 (23):348-352.
5.    Koval’chuk LYa, Vadzyuk SN, Zarudnyy OM, Venher IK, Kostiv SYa, Zarudna OI. Systemic inflammatory response syndrome in atherosclerotic occlusion of aorto-femoro-popliteal segment in the stage of chronic critical ischemia (Ukrainian). Shpytal’na khirurhiya (Ukrainian). 2012;1:5-10.
6.    Koval’chuk LYa, Venher IK, Vayda AR, Kostiv SYa. Preventive reconstruction of the distal anastomosis of the aorta-iliac-femoral aloshunt/prosthesis in distant postoperative period (Ukrainian). Shpytal’na khirurhiya (Ukrainian). 2014;4:26-29.
7.    Kuznecov MR, Koshkin VM, Karalkin AV. Rannie reokljuzii u bol’nyh obliterirujushhim aterosklerozom (Russian). Jaroslavl: Njuans; 2007:176.
8.    Kuznecov MR, Koshkin VM, Komov KV Modern aspects of diagnostics, prevention and treatment of reperfusion syndrome (Russian). Angiol. i sosud. hir. (Russian). 2006;1 (12):133-144.
9.    Kursov SV. The perfusion index in the practice of anesthesiology and intensive care (Russian). Medytsyna nevidkladnykh staniv (Ukrainian). 2015;7:20-26.
10.    Lisin SV, Chadaev AP, Krupatkin AN, Rogov KA, Markov AV, Kozhemjakin SA. State of microcirculation at stage IV chronic arterial insufficiency of the lower limbs atherosclerotic genesis (Russian). Angiol. i sosud. hir. (Russian). 2008;1 (14):21-29.
11.    Ostrovs’ka LO. The effect of surgical central hemodynamics correction upon remodeling of abdominal cavity vessels due to previously modeled aorto-iliac segment occlusion in rats (Ukrainian). Shpytal’na khirurhiya (Ukrainian). 2012;2:53-58.
12.    Petuhov EB, Kuznecov MR, Fedin AI, Virganskij AO, Kuznecova VF, Komov KV, Tepljakov SA, Holopova EA, Sizarev AV, Lisenkov OP, Ibragimov TM. Hemorheological problems when chronic arterial insufficiency of the lower limbs (Russian). Angiol. i sosud. hir. (Russian). 2009;2 (15):13-19.
13.    Rumjanceva SA, Oganov RG, Stupin VA, Silina EV, Orlova AS, Bolevich SB, Afanas’ev VV, Kabaeva EN, Volik SA. Problems and prospects of intermediary metabolism correction  in patients with vascular comorbidity. (Russian). Racional’naja farmakoterapija v kardiologii (Russian). 2013;9(3):316-322.
14.    Rumjanceva SA, Stupin VA, Afanas’ev VV, Silina EV. Algoritmy i shemy terapii zabolevanij, chasto vstrechajushhihsja v klinicheskoj praktike (Russian). Moskva – Sankt-Peterburg: Medicinskaja kniga; 2012:431.
15.    Tarabin AS, Chupin AV. Revascularizing operations in patients with atherosclerotic lesions of the superficial femoral artery (Russian). Angiol. i sosud. hir. (Russian). 2011;1 (17):151-158.
16.    Shevcov VI, Popkov AV, Bunov VS.  Non-reconstruction revascularization operations when limb ischemia (Russian). Angiol. i sosud. hir. (Russian). 2009;2 (15):108-112.
17.    Yakymchuk OA. Prevention of systemic inflammation and reperfusion complications in reconstruction-grafting aorta-hip-popliteal segment segment in patients with chronic critical ischemia. – А manuscript (Ukrainian). Avtoref. kand. med. nauk. (Ukrainian).  Ternopil’: TDMU; 2011:23.
18.    Acar YA, Yamanel L, Cinar O et al. Perfusion index from Pulse Oximetry Predicts Mortality and Correlates with illness Severity Scores in Intensive Care Unit Patients. Acta Medica Mediterranea. 2015;31:237-242.
19.    Beard JD. Which is the best revascularization for critical limb ischemia: Endovascular or open surgery?. J Vasc Surg. 2008;48 (suppl. 6):11-16.
20.    Blaisdell FW. The pathophysiology of skeletal muscle ischemia and the reperfusion syndrome: a review. Cardiovasc Surg. 2002;10(6):620-630.
21.    Flu H, van der Hage JH, Knippenberg B et al. Treatment for peripheral arterial obstructive disease: An appraisal of the economic outcome of complications. J Vasc Surg. 2008;48(2):368-376.
22.    Gleissner CA, Leitinger N, Ley K. Effects of native and modified low-density lipoproteins on monocyte recruitment in atherosclerosis. Hypertension. 2007;50(2):276-283.
23.    Hoiseth LO, Hisdal J, Hoff IE et al. Tissue oxygen saturation and finger perfusion index in central hypovolemia: influence of pain. Critical Care Medicine. 2015;43(4):747-756.
24.    Kabaroudis A, Gerassimidis T, Karamanos D et al. Metabolic alterations of skeletal muscle tissue after prolonged acute ischemia and reperfusion. J Invest Surg. 2003;16(4):219-228.
25.    Klijn E, Groeneveld AB, van Genderen ME et al. Peripheral Perfusion Index Predicts Hypotension during Fluid Withdrawal by Continuous Veno-Venous Hemofiltration in Critically Ill Patients. Blood Purification. 2015;40(1):92-98.
26.    Kukaeva EA, Andrianova M.Iu., Paliulina MV, Mil’chakov V. I. Metabolic aspects of reperfusion syndrome in patients with chronic ischemia of the lower limbs after surgical revascularization. Patol Fiziol Eksp Ter. 2003;4-5 (2):25-27.
27.    Küntscher MV, Kastell T, Altmann J et al. Acute remote ischemic preconditioning II: the role of nitric oxide. Microsurgery. 2002;22(6):227-231.
28.    Kus A, Gurkan Y, Gormus SK et al. Usefulness of perfusion index to detect the effect of brachial plexus block. J Clin Mon Comput. 2013;27(3):325-328.
29.    Liem DA, Verdouw PD, Duncker DJ. Transient limb ischemia induces remote ischemic preconditioning in vivo. Circulation. 2003;107 (24):218-219.
30.    Maksimova Mlu., Fedorova TN. Mildronate in the treatment of transitory ischemic attacks. Zh Nevrol Psikhiatr Im S S Korsakova. 2013;113(6):41-44.
31.    Morsey H, Aslam M, Standfield N. Patients with critical ischemia of the lower limb are at risk of developing kidney dysfunction. Am J Surg. 2003;185(4):360-363.
32.    Rossi M, Carpi A. Skin microcirculation in peripheral arterial obliterative disease. Biomed Pharmacother. 2004;58(8):427-431.
33.    Van Genderen ME, Bartels SA, Lima A et al. Peripheral perfusion index as an early predictor for central hypovolemia in awake healthy volunteers. Anesthesia Analgesia. 2013;116(2):351-356.
34.    Zhu Y, Zhang G, Zhao J et al. Efficacy and safety of mildronate for acute ischemic stroke: a randomized, double-blind, active-controlled phase II multicenter trial. Clin Drug Investig. 2013;33 (10):755-760.

Additional: Article received 20 Jun 2016

The subject of this review is laboratory parameters, which describe molecular mechanisms of arterial ischemia at the vascular wall level — including indicators of the level of cytokines, angiogenesis factors and the state of the vascular intima, lipid metabolism indicators. Specific molecular markers and laboratory tests have been characterized which are used in the evaluation of patients with arterial ischemia. We have briefly listed the indicators of coagulation system and characterized the indicators of anti-coagulation and fibrinolytic systems (soluble fibrin monomer complex (SFMC), D-dimer (fibrin degradation products), plasminogen activation inhibitor type I (PAI-1), plasminogen activator (t-PA)); some biochemical parameters (homocysteine level), lipid profile (cholesterol, LDL, HDL); functions of proinflammatory cytokines and proteins; angiogenesis factors and status of the vascular wall (various types of VEGF, fibroblast factor (FDF), matrix metalloprotease activity, etc.); molecular genetic markers of the risk of arterial ischemia, markers associated with the development of atherosclerosis, hypertension, increased risk of thrombosis. The issue of therapeutic application of certain angiogenic factors has also been briefly highlighted. The conducted analysis of the literature devoted to the laboratory parameters of arterial ischemia leads to the conclusion that at present a large number of molecular mechanisms of this pathology development are known. Many techniques for their study have been developed. Using these parameters enables to estimate the course of the disease and serves as the basis for development of new approaches to early prevention and treatment of arterial ischemia.

Keywords: arterial ischemia, molecular methods of investigation, markers of ischemia, cytokines, factors of angiogenesis.

List of references:  
1.    Belov IV, Stepanenko AB. Povtornye rekonstruktivnye operatcii na aorte i magistralnykh arteriiakh (Russian). Moskva: Meditcinskoe informatcionnoe agentstvo; 2009:7-12.
2.    Voropaev VV, Kovalchuk AV. Choice of method of the repeated reconstructively —restoration operations on aorto —femoral segment at occlusion of vascular explant in remote period (Ukrainian). Naukovii vіsnik Uzhgorods`kogo unіversitetu. Serіia meditcina. «Khіrurgіia» (Ukrainian). 2012;2 (44):33-36.
3.    Gavrilenko TI, Ryzhkova NA, Parhomenko AN Sosudistyi endotelialnyi faktor rosta v clinike vnutrennikh zabolevanii i ego patogeneticheskoe znachenie (Russian) Ukraїnskii kardіologіchnii zhurnal (Ukrainian). 2011;4:87-95.
4.    Gontschar IA, Stepanova JI, Prudyvus IS. Biochemical Predictors and Markers of Ischemic Stroke (Russian). Ed. Prof. V.S. Kamyschnikov. Minsk: Belarusian Medical Academy of Postgraduate Education; 2013:512.
5.    Didenko IP, Gorbunov GN. Prichiny` vy`polneniia povtorny`kh operativny`kh vmeshatel`stv v otdalyonny`e sroki posle rekonstruktivny`kh operatcii` na arteriiakh nizhnikh konechnostei` u bol`ny`kh obliteriruiushchim aterosclerozom (Russian). Vestneyk sankt-peterburgskogo universiteta (Russian). 2008;1:71-77.
6.    Dolgov VV, Svirin PV. Laboratornaia diagnostika narushenii gemostaza (Russian). M.; 2005:356.
7.    Drozhzhin EV, Nikitina YV, Sidorkina ON, Fedorov DA. Dynamic changes in the fibrinolytic system of hemostasis in with syndrome of critical lower limb ischemia (Russian). Sovremennye problemy nauki i obrazovaniia (Russian). 2012;6:194-201.
8.    Eskov VV, Nikitina YV, Dudin NA. Chaotic dynamics of the plasma hemostasis prameters in critical limb ischemia syndrome (Russian). Vestneyk novykh meditcinskikh tekhnologii (Russian). 2013;20(4):12-16.
9.    Zhelankin AV, Sinyov VV, Khasanova ZB, e.a. Mitochondrial haplogroups and subclinical atherosclerosis: a pilot study using roche454 next-generation sequencing technologies (Russian). Patologicheskaia fiziologiia i eksperimentalnaia terapiia (Russian). 2014;1:12-16.
10.    Ivannikova EV, Melkozerov KV, Kalashnikov VY, Terekhin SA, Kononenko IV, Smirnova OM. bFGF and TGFβ1 growth factors, inflammatory markers (IL-6, TNF-α, CRP) and advanced glycation end-products (AGE, RAGE) in patients with ischemic heart disease and type 2 diabetes mellitus (Russian). Kardiologiia. Saharny`i` diabet (Russian). 2013;3:64-70.
11.    Koval SN, Snegurskaya IA, Mysnichenko OV. The vascular endothelial growth factor family and its possible role in the hypertension pathogenesis (Russian). Arterialnaia gipertenziia (Russian). 2012;4 (24):33320.
12.    Koval SN, Miloslavsky DK, Snegurska IA, Schenyavska EN. The Angiogenesis Factors In Internal Diseases (review) (Russian). Vіsnik problem bіologії ta meditcini (Ukrainian). 2012;3, 2(95):11-15.
13.    Lutay MI. Atherosclerosis: contemporary view at pathogenesis (Russian). Ukraїnskii kardіologіchnii zhurnal (Ukrainian). 2004;1:22-34.
14.    Nozadze DN, Balakhonova TV, Sergienko IV, e.a. Lipoprotein-associated phospholipase A2 mass and activity serum levels and carotid atherosclerosis in patients with different categories of cardiovascular risk (Russian). Ateroscleroz i dislipidemii (Russian). 2013;4:39-45.
15.    Nozadze DN, Semenova AE, Kaminnaya VI, Vlasik TN, Sergienko IV. Lipoprotein-associated phospholipase A2 – a new position in the risk stratification? (Russian). Ateroscleroz i dislipidemii (Russian). 2011;1:41-47.
16.    Plotnikov MV, Rizvanov AA, Masgutov RF et al. First results of clinical use of direct gene therapy VEGF and bFGF for treatment of patients with chronic ischemia of lower limbs (Russian). Prakticheskaia meditcina (Russian). Практ мед. 2013;2 (69), № 1-2:123-125.
17.    Plotnikov MV, Kiiasov AP, Maksimov AV et al. Rezultaty primeneniia autologichnykh stvolovykh cletok perifericheskoi krovi u patcientov s khronicheskoi arterialnoi nedostatochnostiu nizhnikh konechnostei (Russian). Angiologiia i sosudistaia hirurgiia (Russian). 2011;2:11-15.
18.    Rogova LN, Shesternina NV, Zamechnik T.V, Fastova IA. Matrix metalloproteinases, their role in physiological and pathological processes (review) (Russian). Vestneyk novykh meditcinskikh tekhnologii (Russian). 2011;ХVIII(2):86-89.
19.    Salafutdinov II, Shafigullina AK, Yalvach ME et al. Effect of simultaneous expression of various usoforms of vascular endothelial growth factor VEGF and fibroblast growth factor FGF2 on proliferation of human umbilical cord blood cells HUVEC (Russian). Cletochnaia transplantologiia i tkanevaia inzheneriia (Russian). 2010;5(2):62-70.
20.    Samko AN, Merkulov EV, Vlasov VM, Filatov DN. Restenosis: causes and mechanisms of development with different types of endovascular treatment (Russian). Ateroscleroz i dislipidemii (Russian). 2014;1:5-8.
21.    Teplyakov AT, Grakova EV, Kalyuzhin VV, e.a. New opportunities for acute decompensated heart failure diagnostics and clinical value of growth factors: vegf, pdgf [ab, fgf basic, tissue inhibitor of metalloproteinase-1, and lipoprotein-associated phospholipase a2 (Russian). Sibirskii meditcinskii zhurnal (Russian). 2015;30(2):50-60.
22.    Archetti S, Martini M, Botteri E et al. Influence of genetic and environmental factors in peripheral arterial disease natural history: Analysis from six years follow up. International Journal of Applied and Basic Medical Research. 2012;2,2:117-122.
23.    Bertoia ML, Pai JK, Cooke JP et al. Plasma homocysteine, dietary B vitamins, betaine, and choline and risk of peripheral artery disease. Atherosclerosis. 2014;July, 235 (1):94-101.
24.    Biselli PM, Guerzoni AR, de Godoy MF et al. Vascular endothelial growth factor genetic variability and coronary artery disease in Brazilian population. Heart Vessels. 2008;23 (6):371-375.
25.    Bruczko M, Wolańska M, Małkowski A et al. Evaluation of Vascular Endothelial Growth Factor and Its Receptors in Human Neointima. Pathobioilogy. 2016;83(1):47-52.
26.    Busuttil RW, Rinderbriecht H, Flesher A et al. Elastase activity: the role of elastase in aortic aneurysm formation. J Surg Res. 1982;32:214-217.
27.    Cao H, Hu X, Zhang Q et al. Homocysteine Level and Risk of Abdominal Aortic Aneurysm: A Meta­­Analysis. PLOS One. 2014;9, Issue 1:85831-85837.
28.    Creutzig A, Lehmacher W, Elze M. Meta­­analysis of randomised controlled prostaglandin E1 studies in peripheral arterial occlusive disease stages III and Vasa. 2004. –Aug, Vol. 33 (3):137-144.
29.    Davis V, Persidskaia R, Baca­­Regen L et al. Matrix metalloproteinase­­2 production and its binding to the matrix are increased in abdominal aortic aneurysm. Arterioscler Thromb Vasc Biol. 1998;18:1625-1633.
30.    Den Heijer M, Lewington S, Clarke R. Homocysteine, MTHFR and risk of venous thrombosis: a meta­­analysis of published epidemiological studies. J Thromb Haemostas. 2005;3:292-299.
31.    Ferrara N. Vascular endothelial growth factor. Arterioscler Thromb Vasc Biol. 2009;29:789-791.
32.    Gupta R. Cell Therapy for Critical Limb Ischemia: Moving Forward One Step at a Time. Circ Cardiovasc Interv. 2011;February 1. 4 (1):1-5.
33.    Halazun KJ, Bofkin KA, Asthana S et al. Hyperhomocysteinaemia is Associated with the Rate of Abdominal Aortic Aneurysm Expansion. Eur J Vasc Endovasc Surg. 2007;33:391-394.
34.    Hickey SE, Curry CJ, Toriello HV. Practice Guideline: lack of evidence for MTHFR polymorphism testing. Genetics in Medicine. 2013;15(2):153-156.
35.    Hoffman M, Monroe D. A cell­­based model of haemostasis. Thromb Haemost. 2001;85:958-965.
36.    Jourdheuil­­Rahmani D, Rolland PH, Rosset E et al. Homocysteine induces synthesis of a serine elastase in arterial smooth muscle cells from multi organ donors. Cardiovasc Res. 1997;34:597-602.
37.    Khandanpour N, Willis G, Meyer FJ et al. Peripheral arterial disease and methylenetetrahydrofolate reductase (MTHFR) C677T mutations: A case­­control study and meta­­analysis. J Vasc Surg. 2009;49(3):711-718.
38.    Kolodgie FD, Burke AP, Skorija KS et al. Lipoprotein­­Associated Phospholipase A2 Protein Expression in the Natural Progression of Human Coronary Atherosclerosis. Arterioscler Thromb Vasc Biol. 2006;Nov:2523-2529.
39.    Marcucci R, Sofi F, Fedi S et al. Thrombophilic risk factors in patients with severe carotid Atherosclerosis. Journal of Thrombosis and Haemostasis. 2005;3:502-507.
40.    Sharp L, Little J. Polymorphisms in genes involved in folate metabolism and colorectal neoplasia: a HuGE review. Am J Epidemiol. 2004;159(5):423-443.
41.    Sofi F, Lari B, Rogolino A et al. Thrombophilic risk factors for symptomatic peripheral arterial disease. J Vasc Surg. 2005;41(2):255-260.
42.    Sun L, Bai Y, Du G. Нарушение функции эндотелия — препятствие для терапевтического ангиогенеза. Therapia. 2011;7/8:68-75.
43.    Takagi H, Manabe H, Kawai N et al. Circulating lipoprotein (a) concentrations and abdominal aortic aneurysm presence. Interactive Cardiovascular and Thoracic Surgery. 2009;9:467-470.
44.    Takeshita S, Pu LQ, Stein LA. Intramuscular administration of vascular endothelial growth factor induces dose­­dependent collateral artery augmentation in a rabbit model of chronic limb ischemia. Circulation. 1994;Nov, 90 (5 Pt 2) II:228-234.
45.    Thompson AR, Drenos F, Hafez H, Humphries SE. Candidate Gene Association Studies in Abdominal Aortic Aneurysm Disease: A Review and Meta­­Analysis. Eur J Vasc Endovasc Surg. 2008;35:19-30.
46.    Witzenbichler B, Asahara T, Murohara T et al. Vascular endothelial growth factor­­C (VEGF­­C/VEGF­­2) promotes angiogenesis in the setting of tissue ischemia. Am J Pathol. 1998;Aug, 153 (2):381-394.
47.    Zintzaras E, Zdoukopoulos N. A Field Synopsis and Meta­­Analysis of Genetic Association Studies in Peripheral Arterial Disease: The CUMAGAS­­PAD Database. Am J Epidemiol. 2009;170:1-11.

Additional: Article received 20 Jun 2016