Regulation of extracellular matrix (ECM) proteins in a model of pressure overload - Effects of ramipril treatment

LVH involves growth of cardiac myocytes as well as remodeling of ECM-components. The aim of this study was to quantitatively examine the effects of ramipnl (RAM) on ECM proteins. LVH was induced in weanling rats by banding of the ascending aorta. Animals were treated with vehicle (n=10), hydralazine (n=10), or ramipril (n=10) during weeks 6-12 after banding. As compared to shams (n=10), relative LV-weight was elevated in the vehicle and hydralazine-treated groups (1.6-1.8-fold). RAM blunted LVH significantly (p<0.001). Using QIA, as compared to sham, vehicleand hydralazine- treated rats revealed a significant increase of cardiac myocyte cell volume (p<0,05}, as well as induction of perivascular {2,5-fold, p<0.01) and interstitial fibrosis (3,5-fold, p< 0,01). In contrast, RAM- treated groups displayed attenuation of hypertrophy and perivascular fibrosis (1,7- and 1,1-fold vs sham, p<0,05 and p=ns), that was significantly lower than in vehicle- and hydralazine-rats (p<0,01, each). Parallel a significant upregulation of Collagen I inRNA (1.9-fold) and Collagen III mRNA ( 2.2-fold) and Laminin B (1.6-fold, p<0.005) was found. Immunohistochemistry revealed that collagen 1 was mainly localized to the extracellular space, collagen IV and laminin to myocyte and endothelial basement membranes, and fibronectm to perivascular and interstitial space. QIA demonstrated that the expression of the examined ECM proteins was markedly increased in vehicle- and hydralazine-rats (2-4-fold vs. shams, p<0,05, each). In hearts of RAM-treated rats collagen I/IV, laminin and fibronectm displayed a similar distribution and quantity as seen in shams. Our data suggest that ACE-inhibition may limit the effects of left ventricular pressure overload on cardiac myocyte hypertrophy, as well as remodeling of ECM components, and fibrosis.