32
HMG-CoA reductase inhibitors have effects that extend beyond cholesterol reduction. We used an angiotensin (Ang) II-dependent model to test the hypothesis that cerivastatin ameliorates cardiac injury. We treated rats transgenic for human renin and angiotensinogen (dTGR) chronically from week 4 to 7 with cerivastatin (0.5 mg/kg/d by gavage). We used immunohistochemistry, electrophoretic mobility shift assays, and RT-PCR techniques. Compared to control dTGR, dTGR treated with cerivastatin had reduced mortality, blood pressure, cardiac hypertrophy, macrophage infiltration, and collagen I and IV deposition. Total plasma cholesterol was not different between the groups. Immunohistochemical analysis showed increased expression of basic fibroblast growth factor (b-FGF), IL-6, and the NF-κB subunit p65 in the media of dTGR, which was markedly reduced by cerivastatin. b-FGF mRNA in the left ventricle was also significantly reduced. The transcription factors NF-κB and AP-1 were substantially less activated in the left ventricle. These results suggest that statins ameliorate Ang II-induced hypertension, cardiac hypertrophy, and remodeling, independent of cholesterol reduction. They suggest that statins interfere with Ang II-induced signaling and transcription factor activation, thereby ameliorating end-organ damage.
Plasma Cholesterol Reduction by Defatted Soy Ontjom (Fermented with Neurospora intermedia) in Rats Fed a Cholesterol-free Diet.
