组织蛋白酶A介导心室缺血/再灌注大鼠的心室远程重塑和心房心肌病

Hohl Mathias, Erb Katharina, Lang Lisa, Ruf Sven, Hübschle Thomas, Dhein Stefan, Linz Wolfgang, Elliott Adrian D, Sanders Prashanthan, Zamyatkin Olesja, Böhm Michael, Schotten Ulrich, Sadowski Thorsten, Linz Dominik

Klinik für Innere Medizin III, Universität des Saarlandes, Homburg/Saar, Germany.

Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany.

JACC Basic Transl Sci. 2019 Jun 24;4(3):332-344. doi: 10.1016/j.jacbts.2019.01.008. eCollection 2019 Jun.

After myocardial infarction, remote ventricular remodeling and atrial cardiomyopathy progress despite successful revascularization. In a rat model of ventricular ischemia/reperfusion, pharmacological inhibition of the protease activity of cathepsin A initiated at the time point of reperfusion prevented extracellular matrix remodeling in the atrium and the ventricle remote from the infarcted area. This scenario was associated with preservation of more viable ventricular myocardium and the prevention of an arrhythmogenic and functional substrate for atrial fibrillation. Remote ventricular extracellular matrix remodeling and atrial cardiomyopathy may represent a promising target for pharmacological atrial fibrillation upstream therapy following myocardial infarction.

心肌梗死后，尽管血管再通成功，但远隔部位的心室重构和心房心肌病仍会进展。在大鼠心室缺血/再灌注模型中，在再灌注时间点开始对组织蛋白酶A的蛋白酶活性进行药理抑制，可防止梗死区域远隔部位的心房和心室发生细胞外基质重构。这种情况与更多存活的心室心肌得以保留以及预防心房颤动的致心律失常和功能基质有关。远隔部位的心室细胞外基质重构和心房心肌病可能是心肌梗死后房颤上游药物治疗的一个有前景的靶点。