Differential Effects of Myocardial Afadin on Pressure Overload-Induced Compensated Cardiac Hypertrophy

Abstract

Background:Pressure overload induces cardiac hypertrophy, which often ends in heart failure. Afadin is an adaptor protein that is ubiquitously expressed and, in the heart, it localizes at intercalated disks. The current study aimed to examine the afadin-mediated cardiac phenotype in mice exposed to different types of pressure overload: transverse aortic constriction (TAC) burden and angiotensin II (Ang II) stimulation.

Methods and Results:Conditional knockout mice with selective deletion of afadin (afadin cKO) in cardiomyocytes were generated. TAC-operated and Ang II-infused mice at 4 weeks had a similar degree of pressure overload and cardiac hypertrophy in the heart. In afadin cKO mice, TAC operation caused progressive left ventricular dysfunction and heart failure, while Ang II infusion did not deteriorate cardiac function. Furthermore, TAC operation produced more fibrosis and apoptosis in the heart than Ang II infusion, and the expression of growth differentiation factor 15, which can promote apoptosis, in the afadin cKO heart was higher in TAC-operated mice than Ang II-infused ones.

Conclusions:In the 2 pressure overload models, myocardial afadin is involved in mechanical stress-induced, but not pharmacological Ang II-related, compensated cardiac hypertrophy.