Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Brazil; Kidney Research Centre, University of Ottawa, Canada; Vascular Biology Center, Medical College of Georgia, Augusta University, United States of America.
Kidney Research Centre, University of Ottawa, Canada.
Life Sci. 2019 Mar 15;221:29-34. doi: 10.1016/j.lfs.2019.01.043. Epub 2019 Feb 2.
Vascular inflammatory responses play an important role in several cardiovascular diseases. Of the many pro-inflammatory vasoactive factors implicated in this process, is aldosterone, an important mediator of vascular oxidative stress. Statins, such as atorvastatin, are cholesterol-lowering drugs that have pleiotropic actions, including anti-oxidant properties independently of their cholesterol-lowering effect. This study investigated whether atorvastatin prevents aldosterone-induced VSMC inflammation by reducing reactive oxygen species (ROS) production. Vascular smooth muscle cells (VSMC) from WKY rats were treated with 1 μM atorvastatin for 60 min or for 72 h prior to aldosterone (10 mol/L) stimulation. Atorvastatin inhibited Rac1/2 and p47phox translocation from the cytosol to the membrane, as well as reduced aldosterone-induced ROS production. Atorvastatin also attenuated aldosterone-induced vascular inflammation and macrophage adhesion to VSMC. Similarly EHT1864, a Rac1/2 inhibitor, and tiron, ROS scavenger, reduced macrophage adhesion. Through its inhibitory effects on Rac1/2 activation and ROS production, atorvastatin reduces vascular ROS generation and inhibits VSMC inflammation. Our data suggest that in conditions associated with aldosterone-induced vascular damage, statins may have vasoprotective effects by inhibiting oxidative stress and inflammation.
血管炎症反应在几种心血管疾病中起着重要作用。在这个过程中涉及到许多促炎血管活性因子，醛固酮是血管氧化应激的重要介质。他汀类药物，如阿托伐他汀，是降低胆固醇的药物，具有多种作用，包括抗氧化特性，而不依赖于其降低胆固醇的作用。本研究旨在探讨阿托伐他汀是否通过降低活性氧（ROS）的产生来预防醛固酮诱导的 VSMC 炎症。用 1μM 阿托伐他汀处理 WKY 大鼠的血管平滑肌细胞（VSMC）60 分钟或 72 小时，然后用醛固酮（10mol/L）刺激。阿托伐他汀抑制 Rac1/2 和 p47phox 从细胞质向膜的易位，并减少醛固酮诱导的 ROS 产生。阿托伐他汀还减弱了醛固酮诱导的血管炎症和巨噬细胞黏附到 VSMC。同样，Rac1/2 抑制剂 EHT1864 和 ROS 清除剂 tiron 也降低了巨噬细胞黏附。通过抑制 Rac1/2 的激活和 ROS 的产生，阿托伐他汀减少了血管 ROS 的生成并抑制了 VSMC 的炎症。我们的数据表明，在与醛固酮诱导的血管损伤相关的情况下，他汀类药物可能通过抑制氧化应激和炎症发挥血管保护作用。
