Telmisartan promotes proliferation and differentiation of endothelial progenitor cells via activation of Akt / 中华医学杂志(英文版)

ABSTRACT

<p><b>BACKGROUND</b>Numerous studies have demonstrated that the peroxisome proliferator-activated receptor-γ (PPARγ) plays an important role in regulating endothelial progenitor cells (EPC) function. Telmisartan, as a partial agonist of PPARγ, may have an effect on the regulation of EPC functions. The purpose of this study was to investigate the effects of telmisartan on EPC proliferation and differentiation.</p><p><b>METHODS</b>Peripheral blood derived mononuclear cells containing EPC were isolated from healthy volunteers and then cultured on fibronectin-coated dishes in the presence or absence of telmisartan. The proliferative activity of EPC was determined by colony forming units (CFU) and MTT assay. The migratory activity of EPC was assessed by transwell assay. The expression of endothelial cells (EC) markers, including vascular endothelial cadherin (VE-cadherin), von Willebrand factor (vWF) and endothelial nitric oxide synthase (eNOS), were measured by Western blotting analysis.</p><p><b>RESULTS</b>Morphological analysis revealed that telmisartan significantly increased the proliferation of EPC and the number of endothelial cell colony forming units. Telmisartan could enhance the expression of the makers of mature EC, including VE-cadherin, vWF, and eNOS, which indicated telmisartan could stimulate EPC to differentiate into mature EC. Telmisartan increased the phosphorylation of Akt in EPC. The inhibition of Akt activation significantly attenuated the effect of telmisartan on EPC functions, suggesting that Akt is involved in the stimulatory effect of telmisartan on EPC differentiation.</p><p><b>CONCLUSIONS</b>The results of this study demonstrate that telmisartan promotes EPC functions via activation of Akt.</p>