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ǥ : ͱ ȣ - 550032   26 
Microarray Analysis in Rat Hearts with Monocrotaline-Induced Pulmonary Hypertension after Simvastatin Treatment
이화여자대학교 의학전문대학원 소아과¹, 흉부외과²
김한울¹ , 손세정¹, 김관창², 홍영미¹
Background and Objectives : Statins offer a novel approach to the treatment of PAH. In addition to lowering cholesterol, statins have been shown to have antiproliferative, antithrombotic, antiinflammatory, and antioxidant effects. Also, simvastatin has been reported to attenuate the development of pulmonary hypertension through increased apoptosis as well as reduced proliferation of smooth muscle cells in obstructive vascular lesions. Microarray experiment can accomplish many genetic tests in parallel. This study evaluated altered expression of genes in rat hearts with monocrotaline(MCT)-induced pulmonary hypertension after simvastatin treatment. Materials and Methods: Six-week-old male rats were grouped as follows: control group, sc injection of saline, MCT group, sc injection of MCT; simvastatin group, sc injection of MCT plus 10 mg/kg/day simvastatin by gavage during all experimental days. Right ventricular pressure, weight, right ventricle/left ventricle+septum ratio in each group were measured. The rats were sacrificed after 28 days. Total RNA was extracted from the rat heart tissue. Processes of fluorescent DNA probe preparation, hybridization, scanning and analysis were undergone in each samples. Results: Administration of simvastatin significantly inhibited the progression of right ventricular hypertrophy on day 28 in the simvastatin group compared with the MCT group. Compared with the control group, MCT was associated with significantly increased expression of 384 genes of biosynthesis(GO:6412, p-value:2.19e-4). And MCT group presented significantly decreased expression of 404 genes of regulation of heart contraction rate. Simvastatin treatment resulted in a significantly increased expression of 670 genes about regulation of progression through cell cycle in the simvastatin group compared to the MCT group. The expression of 598 genes about system development significantly decreased in the simvastatin group compared with the control group. Conclusion : Administration of simvastatin exerted inhibitory effects on RVH during development of MCT induced pulmonary hypertension in rats. Simvastatin changed the expression of genes of system development and regulation of progression through cell cycle in MCT induced pulmonary hypertension rats.


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