Cathepsin A Mediates Ventricular Remote Remodeling and Atrial Cardiomyopathy in Rats With Ventricular Ischemia/Reperfusion

Abstract

Summary: 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. Key Words: atrial cardiomyopathy, atrial fibrillation, ischemia/reperfusion, myocardial infarction, remote remodeling