心筋梗塞後心臓リモデリングに対する筋線維芽細胞へのジメチルセレコキシブの作用の検討

• Published in: 日本薬理学会年会要旨集 p. 1-O-D1-4
• Main Authors: 豊平, 由美子, 松永, 洋明, 瀧口, 知浩, 石兼, 真, 岸上, 赳大, 幾島, 栄悟, 高橋, 富美
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2021
• Subjects: fibroblast; heart
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.94.0_1-O-D1-4

Secretion of extracellular matrix by myofibroblasts, transform from fibroblasts and express alpha smooth muscle actin (aSMA), lead to cardiac fibrosis and progress cardiac remodeling. We previously reported the 2,5-dimethylcelecoxib (DM-C) attenuated cardiac remodeling in different type of cardiac hypertrophy models. However, as the effect of DM-C on myofibroblasts transformation and cardiac remodeling after myocardial infarction (MI) are still unclear, we tried to clarify these points. In in vitro study, dermal fibroblasts from SD rat were used for analysis of myofibroblast transformation. In in vivo study, cryoinjury-induced MI (CMI) mouse model was used. In vitro studies showed that DM-C significantly suppressed the expression of aSMA and the phosphorylation levels of Akt, GSK-3 b and Smad2/3, all of them were elevated by TGF-b treatment. In vivo studies showed that the expression of aSMA and fibrosis area were decreased in DM-C group compared with control group. Further, evaluation of the cardiac function revealed that DM-C-treatment alleviated the reduction of the ejection fraction. These results suggest that DM-C attenuates cardiac remodeling after CMI by inhibiting fibrosis via suppression of the myofibroblast transformation. Therefore, DM-C has potential as the novel drug for treatment of cardiac remodeling after MI.