alexa Attenuation of monocrotaline-induced pulmonary arterial hypertension in rats by rosuvastatin.
Genetics & Molecular Biology

Genetics & Molecular Biology

Journal of Molecular and Genetic Medicine

Author(s): Li XL, Guan RJ, Li JJ

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Abstract BACKGROUND: Although the effects of statins on pulmonary arterial hypertension (PAH) have been studied previously, the results remain uncertain. OBJECTIVE: The aim of this study was to confirm the impacts of rosuvastatin on monocrotaline (MCT)-induced PAH and potential mechanisms. METHODS: Rats were subjected to a single subcutaneous injection of MCT to induce PAH. In the prevention protocol, the rats received different doses of rosuvastatin (2 and 10 mg·kg·d) for 4 weeks since MCT injection, whereas in the treatment protocol, the rats received different doses of rosuvastatin 4 weeks after MCT injection for 4 weeks. At the end of the studies, hemodynamic parameters were measured, and the morphology of small pulmonary arteries (SPAs) and right ventricular hypertrophy were assessed. The expression of proliferating cell nuclear antigen (PCNA) and endothelial nitric oxide synthase (eNOS) in SPAs, and Rho kinase 1 (ROCK-1) and eNOS in lung tissue were determined. RESULTS: Rosuvastatin administration could significantly lower mean pulmonary arterial pressure in both prevention and treatment protocols (P < 0.01, respectively), improve survival after PAH development (P < 0.05), and reduce wall thickening of SPAs and right ventricular hypertrophy (P < 0.01, respectively). At the molecular level, rosuvastatin could inhibit the expression of ROCK-1 (P < 0.05, respectively) and PCNA (P < 0.01, respectively) but restore the expression of eNOS (P < 0.05, respectively). These effects were found in a dose-dependent manner. CONCLUSIONS: The present data confirmed and extended the previous data regarding the protective impacts of statins on PAH. The effects of rosuvastatin seemed to be associated with the regulation of ROCK-1, PCNA, and eNOS expression. This article was published in J Cardiovasc Pharmacol and referenced in Journal of Molecular and Genetic Medicine

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