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

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

Author information

1
Klinik für Innere Medizin III, Universität des Saarlandes, Homburg/Saar, Germany.
2
Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany.
3
Herzzentrum Leipzig Abt. Herzchirurgie, Leipzig, Germany.
4
Centre for Heart Rhythm Disorders, South Australian Health and Medical Research Institute, Royal Adelaide Hospital, University of Adelaide, Adelaide, Australia.
5
Department of Physiology, University of Maastricht, Maastricht, the Netherlands.

Abstract

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.

KEYWORDS:

AF, atrial fibrillation; CatA, cathepsin A; Cx43, connexin 43; ECM, extracellular matrix; I/R, ischemia/reperfusion; ICM, ischemic cardiomyopathy; LA, left atrial; LAD, left anterior descending coronary artery; LV, left ventricular; MRI, magnetic resonance imaging; PL, permanent left anterior descending ligation; SAR, (S)-3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic-acid; atrial cardiomyopathy; atrial fibrillation; ischemia/reperfusion; mRNA, messenger ribonucleic acid; myocardial infarction; remote remodeling

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