- 期刊
- OpenAccess
The direct effects and molecular mechanisms of azilsartan, a new angiotensin AT1-receptor blocker, on the function of high-glucose treated endothelial progenitor cells
摘要
Background: Angiogenesis is impaired in the presence of diabetes mellitus (DM) or hyperglycemia. Endothelial progenitor cells (EPCs), which may play a critical role in vascular repair as well as angiogenesis, have been shown impaired in the presence of clinical DM and hyperglycemia. EPCs could also serve as a potential material for cell therapy in DM related cardiovascular disease. Azilsartan, a new angiotensin AT1-receptor blocker (ARB), was recently approved and is expected to exert a more potent, sustained for 24 h BP-lowering effect compared to existing ARBs. However, the vasculoprotective effects and detailed mechanisms have not been clarified. Aims: This project was conduct to investigate the effects and potential mechanisms of angiotensin AT1-receptor blocking by azilsartan on the function and angiogenesis capability of EPCs. It should be clarified that whether and how azilsartan could improve the function of high-glucose treated EPCs and the EPCs from patients with type 2 DM. Methods: Blood samples were obtained from the peripheral veins of the healthy volunteers or patients with type 2 DM (T2DM) in the morning hours after an overnight fasting. Total mononuclear cells were isolated and cultured with or without high glucose condition to generate late EPCs. Late EPCs from diabetic patients were treated with azilsartan (0.1 and 10μM) or olmesartan, another ARB (0.1 and 10 μM) for 24 hours. Late EPCs from healthy volunteers were treated with high glucose (25mM) for 3 days, and then treated by azilsartan (0.1 or 10μM) with high glucose for one day. The expression of vascular endothelial growth factor (VEGF) and stromal cell-derived factor -1 (SDF-1) were evaluated by Western blotting in cultured EPCs. The effects of azilsartan (0.1 and 10μM) were also examined on human coronary artery endothelial cell (HCAEC) lines. Results: Olmesartan (0.1 and 10μM), but not azilsartan (0.1 and 10μM), dose-dependently increased the expression of VEGF and SDF-1 on late EPCs from T2DM patients. There were also no effects of azilsartan (0.1 and 10μM) on high glucose treated late EPCs from healthy volunteers or on high glucose treated HCAEC. Conclusions: The direct effects of azilsartan on VEGF/ SDF-1 expression of EPCs were different from that of olmesartan, another ARB. Olmesartan but not azilsartan might have better angiogentic effects on EPCs, which should be further proven in in vivo animal studies. However, our findings did provide a potential rational to clinical consideration of ARB therapy for T2DM patients with cardiovascular complications.