Effects of Early and Late Chronic Pressure Overload on Extracellular Matrix Remodeling

The left ventricle (LV) remodels with age and in response to pressure overload. While aging and pressure overload are superimposed in the clinical context, the structural and functional consequences of the individual processes are not well-understood. Accordingly, the objective of this study was to compare the effects of both early and late chronic hypertension on extracellular matrix (ECM) remodeling. The following groups of Dahl rats were studied: 1) young salt-resistant (control, n =6); 2) young salt-sensitive (early phase of chronic hypertension, n =6); 3) middle-aged salt-resistant (aging, n =5); and 4) middle-aged salt-sensitive (late phase of chronic hypertension, n =6). We measured LV mass (LVM) and body weight (BW) and immunoblotted a panel of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and ECM proteins. Total collagen increased, several MMPs decreased, and TIMP-1 increased in the early phase of hypertension, consistent with fibrosis. Active MMP-8 decreased from 8,010±81 U in young salt-resistant to 5,260±313 U in young salt-sensitive ( p