Atorvastatin protects against angiotensin II-induced injury and dysfunction in human umbilical vein endothelial cells through bradykinin 2 receptors.
The morphological and functional integrity of the endothelial cell (EC) is compromised in many cardiovascular diseases such as atherosclerosis, hypertension, and diabetes. Angiotensin II (Ang II) plays important roles in the initiation and progression of these diseases. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) may have cholesterol-independent pleiotropic effects on preventing the EC injury and dysfunction that occurs in these diseases, and the protective effects may relate to bradykinin 2 receptors (B2Rs). Our study was designed to test the hypothesis that atorvastatin, via B2Rs, protects the viability and function of EC exposed to Ang II independent of hemodynamics. The experimental results showed that the cytotoxic effects of Ang II on human umbilical vein endothelial cells were significantly ameliorated by atorvastatin pretreatment (LDH tests, MTT assay, and propdium iodide (PI)/Annexin V-stating analysis), and atorvastatin treatment simultaneously enhanced expression of endothelial nitric oxide synthase and yielded of nitric oxide (NO) and cyclic guanosine monophosphate, but both effects were attenuated by the B2Rs antagonist HOE-140. This study proves the hypothesis and may be pertinent to the complex mechanism of action of statins explaining their long-term beneficial effects in maintaining the morphological and functional integrity of vascular ECs.
Zhang
Xiao-Shan
XS
Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
Ren
Jiang-Hua
JH
Lu
Jing-Ping
JP
Fan
Ying
Y
D000804:Angiotensin II / Q000494:pharmacology* / Q000502:physiology; D017209:Apoptosis; D000069059:Atorvastatin; D002460:Cell Line; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology*; D043782:Receptor, Bradykinin B2 / Q000502:physiology*; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism*
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D043782:Receptor, Bradykinin B2; D000804:Angiotensin II; D000069059:Atorvastatin; D052250:Nitric Oxide Synthase Type III