TGFβ3 exacerbates myocardial remodeling after myocardial infarction

• Published in: Proceedings for Annual Meeting of The Japanese Pharmacological Society Vol. 95; p. 1-O-036
• Main Authors: Tomimatsu, Masashi, Yokota, Kosei, Kominami, Shunsuke, Tanaka, Shota, Maeda, Makiko, Okada, Yoshiaki, Obana, Masanori, Fujio, Yasushi
• Format: Journal Article
• Language: Japanese; English
• Published: Japanese Pharmacological Society 2022
• ISSN: 2435-4953; 2435-4953
• DOI: 10.1254/jpssuppl.95.0_1-O-036

After myocardial infarction (MI), various kinds of cytokines are produced from pro- and/or anti- inflammatory cells that infiltrated into myocardium and contribute to scar formation and/or tissue repair. Among these cytokines, it is widely accepted that TGFβ family performs multiple functions, such as cell proliferation and fibrosis; however, it remains to be fully clarified whether there are functional differences among TGFβ1, 2, and 3. The aim of this study is to elucidate the pathophysiological significance of TGFβ3 after MI. MI was generated by coronary ligation. We measured the expression of TGFβ3 over time after MI by quantitative RT-PCR, and found that the expression of TGFβ3 mRNA peaked 7 days after MI (17.8±12.9 fold v.s non-MI). Quantitative RT-PCR and immunohistological staining showed that TGFβ3 was mainly expressed at the border region of infarction. To examine the effects of TGFβ3 on post-infarct remodeling, we　administered TGFβ3 neutralizing antibody (TGFβ3 nAb) intravenously after MI. Echocardiographic analysis revealed that TGFβ3 nAb reduced cardiac dysfunction (fractional shortening: control IgG;29.8±7.3%, TGFβ3 nAb; 36.9±5.8%). In addition, Masson trichrome staining showed that neutralizing antibodies inhibited cardiac fibrosis after MI. TGFβ3 could promote adverse cardiac remodeling after MI as a novel therapeutic target.