Myocardial Upregulation of Cathepsin D by Ischemic Heart Disease Promotes Autophagic Flux and Protects Against Cardiac Remodeling and Heart Failure.

ABSTRACT:

Background

Lysosomal dysfunction is implicated in human heart failure for which ischemic heart disease is the leading cause. Altered myocardial expression of CTSD (cathepsin D), a major lysosomal protease, was observed in human heart failure, but its pathophysiological significance has not been determined.

Methods and results

Western blot analyses revealed an increase in the precursor but not the mature form of CTSD in myocardial samples from explanted human failing hearts with ischemic heart disease, which is recapitulated in chronic myocardial infarction produced via coronary artery ligation in Ctsd^+/+ but not Ctsd^+/- mice. Mice deficient of Ctsd displayed impaired myocardial autophagosome removal, reduced autophagic flux,

SUBMITTER: Wu P 

PROVIDER: S-EPMC5535800 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature