Departamento de Fisiología, Facultad de Medicina, Universidad Complutense de Madrid and Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
Sci Rep. 2017 Dec 1;7(1):16802. doi: 10.1038/s41598-017-17103-9.
We have investigated whether mineralocorticoid receptor activation can participate in the profibrotic effects of leptin in cardiac myofibroblasts, as well as the potential mechanisms involved. The presence of eplerenone reduced the leptin-induced increase in protein levels of collagen I, transforming growth factor β, connective tissue growth factor and galectin-3 and the levels of both total and mitochondrial of superoxide anion (O) in cardiac myofibroblasts. Likewise, the MEK/ERK inhibitor, PD98059, and the PI3/Akt inhibitor, LY294002, showed a similar pattern. Mitochondrial reactive oxygen species (ROS) scavenger (MitoTempo) attenuated the increase in body weight observed in rats fed a high fat diet (HFD). No differences were found in cardiac function or blood pressure among any group. However, the cardiac fibrosis and enhanced O-levels observed in HFD rats were attenuated by MitoTempo, which also prevented the increased circulating leptin and aldosterone levels in HFD fed animals. This study supports a role of mineralocorticoid receptor in the cardiac fibrosis induced by leptin in the context of obesity and highlights the role of the mitochondrial ROS in this process.
我们研究了醛固酮受体激活是否能参与瘦素在心肌成纤维细胞中的促纤维化作用，以及涉及的潜在机制。依普利酮的存在降低了瘦素诱导的心肌成纤维细胞中Ⅰ型胶原、转化生长因子-β、结缔组织生长因子和半乳糖凝集素-3蛋白水平，以及总超氧化物阴离子（O）和线粒体超氧化物阴离子（O）的水平。同样，MEK/ERK 抑制剂 PD98059 和 PI3/Akt 抑制剂 LY294002 也表现出类似的模式。线粒体活性氧（ROS）清除剂（MitoTempo）减弱了高脂饮食（HFD）喂养大鼠体重的增加。各组之间的心脏功能或血压没有差异。然而，MitoTempo 减弱了 HFD 大鼠的心脏纤维化和增强的 O 水平，同时也防止了 HFD 喂养动物循环中瘦素和醛固酮水平的升高。这项研究支持在肥胖背景下，醛固酮受体在瘦素诱导的心脏纤维化中的作用，并强调了线粒体 ROS 在这一过程中的作用。
