Peng Shih-Yuan, Tsai Cheng-Hsuan, Wu Xue-Ming, Huang Hsin-Hsiu, Chen Zheng-Wei, Lee Bo-Ching, Chang Yi-Yao, Pan Chien-Ting, Wu Vin-Cent, Chou Chia-Hung, Hung Chi-Sheng, Liao Che-Wei, Lin Yen-Hung
Department of Internal Medicine, Division of Cardiology, College of Medicine, National Taiwan University Hospital, National Taiwan University, Taipei 100, Taiwan.
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
Biomedicines. 2022 May 12;10(5):1119. doi: 10.3390/biomedicines10051119.
Excessive aldosterone secretion causes endothelial dysfunction, vascular inflammation, and vascular fibrosis in patients with primary aldosteronism (PA). Endothelial function is closely related to endothelial mitochondria. However, the effects of elevated aldosterone levels on endothelial mitochondria remain unclear. In this study, we used primary cultured human umbilical vein endothelial cells (HUVECs) to investigate the effects of aldosterone on endothelial mitochondria. Mineralocorticoid receptor (MR) small interfering (si)RNA or glucocorticoid receptor (GR) siRNA were used to confirm the pathway by which aldosterone exerts its effects on the mitochondria of HUVECs. The results showed that excess aldosterone suppressed mitochondrial DNA copy numbers, anti-mitochondrial protein, and SOD2 protein expression in a dose- and time-dependent manner. These effects were attenuated by treatment with MR siRNA, but not with GR siRNA. Furthermore, it was attenuated by treatment with a mitochondria-targeted antioxidant (Mito-TEMPO, associated with mitochondrial reactive oxygen species (ROS) production), but not N-acetyl-L-cysteine (associated with cytosolic ROS production), which suggests that the process was through the mitochondrial ROS pathway, but not the cytosolic ROS pathway. In conclusion, aldosterone excess suppressed endothelial mitochondria through the MR/mitochondrial ROS pathway.
原发性醛固酮增多症（PA）患者中，醛固酮分泌过多会导致内皮功能障碍、血管炎症和血管纤维化。内皮功能与内皮线粒体密切相关。然而，醛固酮水平升高对内皮线粒体的影响仍不清楚。在本研究中，我们使用原代培养的人脐静脉内皮细胞（HUVECs）来研究醛固酮对内皮线粒体的影响。使用盐皮质激素受体（MR）小干扰（si）RNA或糖皮质激素受体（GR）siRNA来确认醛固酮对HUVECs线粒体发挥作用的途径。结果表明，过量醛固酮以剂量和时间依赖性方式抑制线粒体DNA拷贝数、抗线粒体蛋白和SOD2蛋白表达。这些作用通过MR siRNA处理而减弱，但GR siRNA处理则无此效果。此外外此外，线粒体靶向抗氧化剂（Mito-TEMPO，与线粒体活性氧（ROS）产生相关）处理可使其减弱，而N-乙酰-L-半胱氨酸（与胞质ROS产生相关）处理则无此效果，这表明该过程是通过线粒体ROS途径，而非胞质ROS途径。总之，醛固酮过量通过MR/线粒体ROS途径抑制内皮线粒体。
