Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Pathophysiology, Nanjing Medical University, 818 Tianyuan Dong Road, Nanjing 211166, Jiangsu, China.
Department of Pharmacy, The Binhu Hospital of Hefei, Hefei, Anhui, China.
Sci Rep. 2017 Mar 14;7:44638. doi: 10.1038/srep44638.
AS-1, the TIR/BB loop mimetic, plays a protective role in cardiac ischemia/reperfusion (I/R) but the molecular mechanism remains unclear. The muscle specific caveolin3 (Cav-3) and the caveolae have been found to be critical for cardioprotection. This study aimed to evaluate our hypothesis that caveolae and Cav-3 are essential for AS-1-induced cardioprotection against myocardial I/R injury. To address these issues, we analyzed the involvement of Cav-3 in AS-1 mediated cardioprotection both in vivo and in vitro. We demonstrate that AS-1 administration significantly decreased infarct size, improved cardiac function after myocardial I/R and modulated membrane caveolae and Cav-3 expression in the myocardium. For in vitro studies, AS-1 treatment prevented Cav-3 re-distribution induced by H/R injury. In contrast, disruption of caveolae by MCD treatment or Cav-3 knockdown abolished the protection against H/R-induced myocytes injury by AS-1. Our findings reveal that AS-1 attenuates myocardial I/R injury through caveolae and Cav-3 dependent mechanism.
AS-1，TIR/BB 环类似物，在心肌缺血/再灌注（I/R）中发挥保护作用，但分子机制尚不清楚。已经发现肌肉特异性 caveolin3（Cav-3）和 caveolae 对于心脏保护至关重要。本研究旨在评估我们的假设，即 caveolae 和 Cav-3 对于 AS-1 诱导的心肌 I/R 损伤的心脏保护作用是必不可少的。为了解决这些问题，我们分析了 Cav-3 在 AS-1 介导的心脏保护中的作用，包括体内和体外研究。我们证明，AS-1 给药可显著减少梗死面积，改善心肌 I/R 后的心脏功能，并调节心肌中膜 caveolae 和 Cav-3 的表达。在体外研究中，AS-1 处理可预防 H/R 损伤引起的 Cav-3 重分布。相反，MCD 处理或 Cav-3 敲低破坏 caveolae 会消除 AS-1 对 H/R 诱导的心肌细胞损伤的保护作用。我们的研究结果表明，AS-1 通过 caveolae 和 Cav-3 依赖性机制减轻心肌 I/R 损伤。
