DOI 10.1007/s10517-017-3630-4 Bulletin of Experimental Biology and Medicine, Vol. 162, No. 10, February, 2017
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GENERAL PATHOLOGY AND PATHOPHYSIOLOGY Cystatin C as a Marker of Progressing Cardiovascular Events during Coronary Heart Disease
M. M. Gevorgyan1, N. P. Voronina2, N. V. Goncharova1, T. V. Kozaruk2, G. S. Russkikh1, L. A. Bogdanova3, and T. A. Korolenko1 Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 162, No. 10, pp. 413-416, October, 2016 Original article submitted May 22, 2015 The role of cystatin C, an inhibitor of cysteine proteases, as an alternative and potent predictor of acute cardiovascular events in coronary heart disease (CHD) patients was examined and compared to that of other markers of cardiorenal abnormalities. The patients with CHD demonstrated elevated serum cystatin C, especially in cases with serious risk of cardiovascular complications. In comparison with other indicators of cardiorenal dysfunction, cystatin C can be viewed as an alternative predictor of cardiovascular complications, although its sensitivity is inferior to that of high-sensitivity C-reactive protein and natriuretic peptide. Key Words: cystatin C; coronary heart disease; biochemical markers; clinical study The search for novel biological markers and predictors of complications in patients with cardiovascular diseases is an important problem in the early diagnosis and monitoring the treatment effectiveness [14,9]. To solve this task, clinical proteomics advanced promising biomarkers of cardiovascular diseases used to reveal atherosclerosis and hypertension [5,7,8]. It also examines some non-lipid chemicals, e.g. cystatin C, a promising inhibitor of cysteine proteases used to assess the severity of cardiorenal syndrome and to reveal the atherosclerosis risk group among middleaged patients [13-15]. Comparative analysis is carried out to assess possible role of some non-lipid agents (precursor of brain natriuretic peptide NT-proBNP, cystatin C, etc.) as the risk factors of acute cardiovascular complications and predictors of restenosis after coronary stenting [6]. At present, association of these indices with inflammatory markers of atherosclerosis such as high-sensitivity CResearch Institute of Physiology and Fundamental Medicine; 2Research Institute of Biochemistry; 3Research Institute of Molecular Pathology and Pathomorphology, Novosibirsk, Russia. Address for correspondence:
[email protected]. T. A. Korolenko
1
reactive protein (hs-CRP) and their correlation with disturbances in blood serum and with the local abnormalities in atherosclerotic plaques were not examined comprehensively [10-12]. Moreover, little is known about interrelations of the above non-lipids with established lipid markers of atherosclerosis and some inflammatory biomarkers. Cystatins are endogenous low-molecular-weight proteins with basic function related to inhibition of cysteine proteases and control of proteolysis [2,3,9]. There are three types of cystatins: intracellular (cystatins A and B), extracellular (cystatins C, S, SA, SN, etc.), and high- and low-molecular-weight kininogens [4,15]. Cystatin C is the most studied cystatin [3,4,15]. It is involved in aging, cell death, degradation of proteins in extracellular matrix, cell differentiation, proliferation and migration of some cell types, synthesis of interleukins and NO, as well as in antigen processing and presentation [4]. This work was designed to evaluate the possibility of using cystatin C as the low-molecular non-lipid biomarker and risk factor of acute cardiovascular events in CHD patients.
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Bulletin of Experimental Biology and Medicine, Vol. 162, No. 10, February, 2017 GENERAL PATHOLOGY AND PATHOPHYSIOLOGY
MATERIALS AND METHODS The study had been carried out in Novosibirsk Municipal Outpatient Clinic No. 1. All patients gave informed consent for collection of biological specimens and their use. The control group comprised 54 patients (age 6075 years) with diffuse dorsopathy at the remission stage not accompanied by changes in the blood lipid profile and without history of coronary heart disease (CHD). The experimental group consisted of age-matched patients with CHD (n=62). In both groups, blood level of NT-proBNP, a biomarker of cardiac failure and indicator of its severity, was measured on an EFOS 9305 semi-automated immunoassay analyzer (Sapfir). According to the results, the experimental patients were subdivided into 2 subgroups: in subgroup A (n=39), NT-proBNP concentration was 271.6±50.3 pg/ml, and in group B patients with high risk of fatal outcome, the concentration of this peptide was 1354.0±319.2 pg/ml. Cystatin C was assayed by immunoturbidimetry using Cystatin C-AT and Aqua-Test kits. The method is based on the use of colloidal gold particles coated with polyclonal antibodies against human cystatin C. The concentrations of creatinine, urea, and hs-CRP as well as the lipid profile and activities of lactate dehydrogenase (LDH), creatine phosphokinase (CPK), and creatine phosphokinase isoenzyme CPK-MB were measured using the appropriate kits (Beckman Coulter).
The data were analyzed statistically using Statistica 10.0 software and ANOVA dispersion analysis. Distribution of the samples was established with q-q plot and Kolmogorov—Smirnov fitting criterion. Significance was assessed with the parametric Student’s t test, non-parametrical Mann—Whitney U-test, and Pearson and Spearman correlation tests at p
