Abstract:

Objective   To observe the effect of metformin on type 1 angiotensin II receptor （AT1R）expression in endothelial cells and investigate its mechanism. Methods     AT1R, inhibitor protein κB （I-κB）and AMP-activated protein kinase α(AMPKα ) protein expressions in endothelial cells were determined by Western blot, and nuclear factor-κB (NF-κB) activation in endothelial cells was observed by con-focal laser scanning microscopy. The lactate dehydrogenase (LDH) activation in the culture medium was detected by colorimetric assay. Also, the roles of NFκB and AMPKα in the effect of metformin on AT1R were determined by RNA interference technology. Results    I-κB phosphorylation and AT1R protein expression induced by tumor necrosis factor α (TNFα) in endothelial cells were significantly reduced by metformin, and  LDH activity in the endothelial cell culture medium was significantly decreased (P<0.01). The inhibitory effect of metformin on AT1R expression in endothelial cells was significantly reversed by AMPKαSiRNA (P<0.01). Conclusion    NF-κB activation and AT1R expression can be inhibited by the intervention of metformin, and activation of the AMPKα pathway plays an important role in the beneficial effect of metformin on cardiovascular endothelial cells.

Key words: Metformin；Endothelial cells;  Type 1 angiotensin II receptor; AMP-activated protein kinase α; Nuclear factor-κB