3-HMG-Coenzyme A reductase inhibition and extracellular matrix gene expression in the pressure-overloaded rat heart.

The purpose of this study was to determine whether 3-HMG-Coenzyme A (HMG-CoA) reductase inhibition would attenuate the early pressure overload-induced activation of extracellular matrix genes in the left ventricle (LV) of the heart. Sprague-Dawley rats were randomized to 1 of 4 treatment groups: sham-operation+vehicle (SH-V), aortic constriction+vehicle (AC-V), AC+rosuvastatin (RSV, 2 mg/kg; AC-LO), and AC+RSV (10 mg/kg; AC-HI). Rats were injected with normal NaCl (V) or RSV once daily, beginning 1 day before surgery, and killed 1 or 3 days after surgery. Hemodynamic measurements were made in the open-chest anesthetized state. LV levels of transforming growth factor beta1 (TGF-beta1), procollagen 1 (C1), and fibronectin (FN) mRNA were measured by Northern blotting. AC induced a approximately 25% increase in LV weight after 3 days that was not altered by RSV treatment. LV expression of TGF-beta1, C1, and FN mRNA was approximately 2-fold, approximately 2.5-fold, and approximately 5-fold greater, respectively, in hearts of AC-V compared to SH-V rats 3 days post-operation, and was not significantly decreased by either dose of RSV. Inhibition of HMG-CoA reductase does not attenuate the pronounced aortic constriction-induced increases in the early expression of TGF-beta1, C1, and FN in this model of acute pressure overload of the rat heart.