Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
The Zena and Michael A. Wiener CVI, Icahn School of Medicine at Mount Sinai, New York, USA.
Sci Rep. 2017 Sep 27;7(1):12343. doi: 10.1038/s41598-017-11985-5.
Reperfusion alters post-myocardial infarction (MI) healing; however, very few systematic studies report the early molecular changes following ischemia/reperfusion (I/R). Alterations in the remote myocardium have also been neglected, disregarding its contribution to post-MI heart failure (HF) development. This study characterizes protein dynamics and contractile abnormalities in the ischemic and remote myocardium during one week after MI. Closed-chest 40 min I/R was performed in 20 pigs sacrificed at 120 min, 24 hours, 4days, and 7days after reperfusion (n = 5 per group). Myocardial contractility was followed up by cardiac magnetic resonance (CMR) and tissue samples were analyzed by multiplexed quantitative proteomics. At early reperfusion (120 min), the ischemic area showed a coordinated upregulation of inflammatory processes, whereas interstitial proteins, angiogenesis and cardio-renal signaling processes increased at later reperfusion (day 4 and 7). Remote myocardium showed decreased contractility at 120 min- and 24 h-CMR accompanied by transient alterations in contractile and mitochondrial proteins. Subsequent recovery of regional contractility was associated with edema formation on CMR and increases in inflammation and wound healing proteins on post-MI day 7. Our results establish for the first time the altered protein signatures in the ischemic and remote myocardium early after I/R and might have implications for new therapeutic targets to improve early post-MI remodeling.
再灌注会改变心肌梗死后（MI）的愈合情况；然而，很少有系统的研究报告缺血/再灌注（I/R）后早期的分子变化。还忽略了对远程心肌的改变，忽视了其对 MI 后心力衰竭（HF）发展的贡献。本研究在 MI 后一周内，对缺血和远程心肌中的蛋白质动态和收缩异常进行了特征描述。在 20 头猪中进行了 40 分钟的闭胸 I/R，然后在再灌注后 120 分钟、24 小时、4 天和 7 天处死（每组 n = 5）。通过心脏磁共振（CMR）监测心肌收缩力，并通过多重定量蛋白质组学分析组织样本。在早期再灌注（120 分钟）时，缺血区域显示出炎症过程的协调上调，而在晚期再灌注（第 4 天和第 7 天）时，间质蛋白、血管生成和心脏肾脏信号通路过程增加。在 120 分钟和 24 小时的 CMR 中，远程心肌的收缩力下降，同时收缩蛋白和线粒体蛋白发生短暂改变。随后的区域性收缩力恢复与 CMR 上的水肿形成以及 MI 后第 7 天炎症和伤口愈合蛋白的增加有关。我们的研究结果首次建立了 I/R 后早期缺血和远程心肌中改变的蛋白质特征，这可能对改善 MI 后早期重塑的新治疗靶点具有重要意义。
