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Relation of osteoprotegerin level and numerous of circulating progenitor mononuclears in patients with metabolic syndrome

Alexander E. Berezin, Alexander A Kremzer, Tatyana A Berezina, Yulia V Martovitskaya, Elena A Gromenko.


The aim of the study: to investigate whether an elevated level of osteoprotegerin (OPG) predicts imbalance between different phenotypes of circulating endothelial (EPCs) and mononuclear (MPCs) progenitor cells in patients with MetS. Methods: Forty seven patients with MetS and 35 healthy volunteers were prospectively evolved in the study 47 between February 2013 and November 2013. We enrolled MetS subjects without known CV disease including angina pectoris, asymptomatic atherosclerosis (negative contrast-enhanced multispiral tomography angiography). MetS was diagnosed based on the National Cholesterol Education Program Adult Treatment Panel III criteria. All patients have given their informed written consent for participation in the study. Results: The mean serum level of OPG was significantly higher among entire MetS patients’ cohort compared to the healthy volunteers (1142 ± 186 pg/mL in MetS group vs. 245 ± 75 pg/mL in control group; p < 0.001). Patients with MetS were divided in to two subgroups depended on serum level of OPG using mean value as cutoff point. Subjects with OPG level < 1142 pg/mL and ≥ 1142 pg/mL were included in cohorts with lower (n=18) and higher (n=29) OPG level, respectively.Multivariate regression analysis adjusted age, sex and BMI has shown that OPD related negatively with numbers of CD14+/CD309+ cells (r = -0.505, P = 0.001), CD14/CD309/Tie2+ (= -0.510, P = 0.001), CD45-/CD34+ cells (r = -0.298, P = 0.001), triglycerides (r = -0.22, P = 0.001), hs-CRP (r = -0.24, P = 0.001), dyslipidemia (r = -0.301, P = 0.001), LDL cholesterol (r = -0.288, P = 0.002), soluble receptor activator of nuclear factor kappa-B ligand (r = -0.303, P = 0.001), serum uric acid (r = -0.218, P < 0.001), and positively related with galectin-3 (r =0.41, P = 0.001), HOMA-IR (r = 0.306, P = 0.001), The MetS Z score at +1.0 SD (r =0.262, P = 0.001), Framingham risk score (r = 0.254, P = 0.001). In multivariate logistic regression analysis we found that OPG, dyslipidemia, galectin-3, and HOMA-IR were independent predictors for depletion in numerous of circulating EPCs and MPCs alone, as well as combined variable: EPCs and MPCs. The comparison of predictive models based on several biomarkers including dyslipidemia, galectin-3, and HOMA-IR has shown a lack of advantages of these models versus predictive model constructed on OPG alone. Conclusion: We found the elevated OPG level in MetS patients without known CV disease predicted declined numerous of both EPCs and MPCs beyond traditional CV risk factors.

Key words: Metabolic syndrome; osteoprotegerin; endothelial-derived progenitor cells, mononuclear-derived progenitor cells.

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