School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, China ; and.
Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China .
J Cardiovasc Pharmacol. 2024 May 1;83(5):410-432. doi: 10.1097/FJC.0000000000001544.
Cardiac fibrosis is considered as unbalanced extracellular matrix production and degradation, contributing to heart failure. Short-chain acyl-CoA dehydrogenase (SCAD) negatively regulates pathological cardiac hypertrophy. The purpose of this study was to investigate the possible role of SCAD in cardiac fibrosis. In vivo experiments were performed on spontaneously hypertensive rats (SHR) and SCAD-knockout mice. The cardiac tissues of hypertensive patients with cardiac fibrosis were used for the measurement of SCAD expression. In vitro experiments, with angiotensin II (Ang II), SCAD siRNA and adenovirus-SCAD were performed using cardiac fibroblasts (CFs). SCAD expression was significantly decreased in the left ventricles of SHR. Notably, swim training ameliorated cardiac fibrosis in SHR in association with the elevation of SCAD. The decrease in SCAD protein and mRNA expression levels in SHR CFs were in accordance with those in the left ventricular myocardium of SHR. In addition, SCAD expression was downregulated in CFs treated with Ang II in vitro, and SCAD siRNA interference induced the same changes in cardiac fibrosis as Ang II-treated CFs, while adenovirus-SCAD treatment significantly reduced the Ang II-induced CFs proliferation, alpha smooth muscle actin (α-SMA), and collagen expression. In SHR infected with adenovirus-SCAD, the cardiac fibrosis of the left ventricle was significantly decreased. However, cardiac fibrosis occurred in conventional SCAD-knockout mice. SCAD immunofluorescence intensity of cardiac tissue in hypertensive patients with cardiac fibrosis was lower than that of healthy subjects. Altogether, the current experimental outcomes indicate that SCAD has a negative regulatory effect on cardiac fibrosis and support its potential therapeutic target for suppressing cardiac fibrosis.
心肌纤维化被认为是细胞外基质产生和降解的失衡，导致心力衰竭。短链酰基辅酶 A 脱氢酶（SCAD）负调控病理性心肌肥大。本研究旨在探讨 SCAD 在心肌纤维化中的可能作用。在自发性高血压大鼠（SHR）和 SCAD 敲除小鼠中进行了体内实验。使用高血压伴心肌纤维化患者的心脏组织测量 SCAD 的表达。在体外实验中，使用血管紧张素 II（Ang II）、SCAD siRNA 和腺病毒-SCAD 处理心肌成纤维细胞（CFs）。SHR 的左心室中 SCAD 的表达明显降低。值得注意的是，游泳训练改善了 SHR 的心肌纤维化，同时升高了 SCAD。SHR CFs 中的 SCAD 蛋白和 mRNA 表达水平降低与 SHR 左心室心肌中的表达降低一致。此外，体外 Ang II 处理下调了 CFs 中的 SCAD 表达，SCAD siRNA 干扰诱导的 CFs 纤维化变化与 Ang II 处理的 CFs 相同，而腺病毒-SCAD 处理可显著减少 Ang II 诱导的 CFs 增殖、α平滑肌肌动蛋白（α-SMA）和胶原表达。在感染腺病毒-SCAD 的 SHR 中，左心室心肌纤维化明显减少。然而，在常规 SCAD 敲除小鼠中发生了心肌纤维化。高血压伴心肌纤维化患者心脏组织中的 SCAD 免疫荧光强度低于健康受试者。总之，目前的实验结果表明，SCAD 对心肌纤维化具有负调控作用，支持其作为抑制心肌纤维化的潜在治疗靶点。
