Age‐dependent alterations to the cardiac extracellular matrix in heart failure: differences between ventricular and atrial remodeling

Abstract

Structural remodeling of the ventricles and the atria are features of both myocardial disease and aging and the extracellular matrix (ECM) plays a pertinent role in this process. This study sought to determine if aging exacerbates structural remodeling of the myocardium in heart failure (HF).HF was induced in young (18 months) and old (>8 years) sheep by ventricular tachypacing. Echocardiography was performed consciously and collagen content assessed histologically. Matrix metalloproteinases (MMPs) were quantified by gelatin zymography whereas tissue inhibitor of metalloproteinases (TIMPs) were assessed by immunoblotting.HF led to left ventricular (LV) dilatation and reduced contractility in both young and old animals, although changes were more pronounced in old. In contrast, HF increased left atrial (LA) diameter to a similar extent in both groups. Age‐associated changes to LV ECM remodeling occurred in HF with collagen accumulation in young and depletion in old. In the LA however, fibrosis was present with HF in both young and old animals. LV MMP‐2 activity was elevated in young HF but to no greater extent in old HF, however TIMP levels were reduced only in aged HF. In the LA, MMP‐2:TIMP ratio was elevated in both young and old HF.This study demonstrates that age‐dependent alterations to LV ECM remodeling occur in HF, but HF‐induced remodeling of the LA is largely unaffected by age.Funded by BHF and EU “Normacor”.