The effect of angiotensin ii receptor blocker valsartan on the level of circulating endothelial progenitor cells in diabetic patients with chronic heart failure

O. O. Kremzer


Reduction of circulating endothelial progenitor cells (EPCs) are considered as strong and robust biomarkers for prediction of cardiovascular outcomes in both chronic heart failure and diabetic populations. The aim of this study was to assess the effect of angiotensin II receptor blocker valsartan on the circulating level of endothelial progenitor cells in patients with ischemic chronic heart failure and type two diabetes mellitus (T2DM). The study population was structured retrospectively after determining coronary artery disease by multispiral computed tomography / contrast enhanced angiography in 126 subjects with chronic heart failure. Blood samples were taken at baseline before valsartan given and in 52 weeks after study entry. Endothelial progenitor cell populations were phenotyped by flow cytofluorimetry by means of monoclonal antibodies labeled with fluorochromes. Proangiogenic circulating EPCs were identified as CD45-CD34+. CD133, СD309 (VEGFR2), and Tie-2 antigens were also determined to identify subpopulations of EPCs coexpressing CD14 antigen. All subjects were distributed into two cohorts depending on daily doses of valsartan. Low (80-160 mg daily orally) and high doses (240-320 mg daily orally) of valsartan were used, and they were adjusted depending on achievement of the blood pressure level less than 140/80 mm Hg. The finding may suggest that the positive effect of valsartan on the endothelial function might be implemented by involving EPCs in reparative processes of vasculature in subjects with ischemic chronic heart failure with T2DM and thereby to improve the long-term prognosis in this patient population. The change from baseline in CD34+ subset of EPCs (frequencies and absolute values) was not significantly different between treatment cohorts. There was a significant increase of the circulating level of CD14+CD309+cells in two patient cohorts. But more prominent change of CD14+CD309+cells was observed in subjects who were given valsartan in high daily doses when compared with persons who were included into the cohort with low daily doses of the drug (P<0.05). Therefore, both frequencies and absolute values in CD14+CD309+Tie2+ were increased significantly in patients who were treated with high doses of valsartan only. A positive influence of angiotensin II receptor blocker valsartan in escalation doses on bone marrow-derived EPCs phenotyped as CD14+CD309+ and CD14+CD309+Tie2+ in patients with ischemic chronic heart failure and T2DM has been found.


coronary heart disease; diabetes; heart failure; endothelial progenitor cells; valsartan

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