Korean Circ J. 2011 Sep;41(9):518-27. doi: 10.4070/kcj.2011.41.9.518. Epub 2011 Sep 29.

Changes of pulmonary pathology and gene expressions after simvastatin treatment in the monocrotaline-induced pulmonary hypertension rat model.

Korean circulation journal

Yun Hee Lee, Kwan Chang Kim, Min-Sun Cho, Young Mi Hong

PMID: 22022327 PMCID: PMC3193043 DOI: 10.4070/kcj.2011.41.9.518

Abstract

BACKGROUND AND OBJECTIVES: Simvastatin's properties are suggestive of a potential pathophysiologic role in pulmonary hypertension. The objectives of this study were to investigate changes of pulmonary pathology and gene expressions, including endothelin (ET)-1, endothelin receptor A (ERA), inducible nitric oxide synthase (NOS2), endothelial nitric oxide synthase (NOS3), matrix metalloproteinase (MMP) 2, tissue inhibitor of matrix metalloproteinases (TIMP) and caspase 3, and to evaluate the effect of simvastatin on monocrotaline (M)-induced pulmonary hypertension.

MATERIALS AND METHODS: Six week old male Sprague-Dawley rats were treated, as follows: control group, subcutaneous (sc) injection of saline; M group, sc injection of M (60 mg/kg); and simvastatin group, sc injection of M (60 mg/kg) plus 10 mg/kg/day simvastatin orally.

RESULTS: On day 28, right ventricular hypertrophy (RVH) significantly decreased in the simvastatin group compared to the M group. Similarly, right ventricular pressure significantly decreased in the simvastatin group on day 28. From day 7, the ratio of medial thickening of the pulmonary artery was significantly increased in the M group, but there was no significant change in the simvastatin group. The number of muscular pulmonary arterioles was significantly reduced in the simvastatin group. On day 5, gene expressions of ET-1, ERA, NOS2, NOS3, MMP and TIMP significantly decreased in the simvastatin group.

CONCLUSION: Administration of simvastatin exerted weak inhibitory effects on RVH and on the number of muscular pulmonary arterioles, during the development of M-induced pulmonary hypertension in rats. Simvastatin decreased gene expressions on day 5.

Keywords: Gene expression; Hypertension, pulmonary; Monocrotaline; Simvastatin

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