Spatio-temporal Regulation of Calpain Activity After Experimental Myocardial Infarction in Vivo

Overview

Journal Biochem Biophys Rep

Specialty Biochemistry

Date 2021 Nov 11

PMID 34761128

Citations 5

Authors

Kun Zhang

Melissa M Cremers

Stephan Wiedemann

David M Poitz

Christian Pfluecke

Frank R Heinzel

Burkert Pieske

Volker Adams

Antje Schauer

Robert Winzer

Ruth H Strasser

Axel Linke

Silvio Quick

Felix M Heidrich

Affiliations

Soon will be listed here.

Abstract

Background: Calpains are calcium activated cysteine proteases that play a pivotal role in the pathophysiology of cardiac remodeling.

Methods: Here, we performed left anterior descending coronary artery ligation in rats as a model for ischemic systolic heart failure and examined the time- and region-specific regulation of calpain-1 and calpain-2 in the left ventricular myocardium.

Results: Following anterior wall myocardial infarction, calpain activity was significantly increased restricted to the ischemic anterior area at days 1, 5 and 14. No changes in calpain activity at neither time point were detected in the borderzone and remote posterior area of the left ventricle. Of note, calpain activity in the infarcted anterior myocardium was regulated differentially in the acute vs. subacute and chronic phase. In the acute phase, calpain translocation to the plasma membrane and attenuation of the expression of its endogenous inhibitor, calpastatin, were identified as the driving forces. In the subacute and chronic phase, calpain activity was regulated at the level of protein expression that was shown to be essentially independent of transcriptional activity.

Conclusions: We conclude that myocardial infarction leads to a distinct calpain regulation pattern in the left ventricular myocardium that is region specific and time dependent. Considering the results from our previous studies, a spatio-temporal interaction between calpains and calcium dependent natriuretic peptide production in the infarcted myocardium is possible.

General Significance: Our results shed more light in the differential regulation of calpain activity in the myocardium and might aid in the development of targeted post-infarct and/or heart failure therapeutics.

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