Degenerative therapy for heart failure using autologous myocardial fibroblast.

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590482
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Osaka University
• Principal Investigator: KAWAGUCHI Naomasa 大阪大学, 医学(系)研究科(研究院), 准教授 (70224748)
• Co-Investigator(Kenkyū-buntansha): MORI Seiji 大阪大学, 大学院医学系研究科, 准教授 (90467506) ; HAMADA Yoshinosuke 大阪大学, 大学院医学系研究科, 准教授 (10362683) ; MATSUURA Nariaki 大阪大学, 大学院医学系研究科, 教授 (70190402)
• Co-Investigator(Renkei-kenkyūsha): MIYAGAWA Sigeru 大阪大学, 大学院医学系研究科, 准教授 (70544237)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 再生医学

Outline of Final Research Achievements

We examined the effects of tissue inhibitors of metalloproteinases (TIMPs) on cardiac fibroblasts (CFs) and cardiomyocytes(CM). In vitro, TIMP-1～-4 enhanced smooth muscle actin (SMA) expression in CFs, and TIMP-1 and TIMP-3 enhanced the expression of phosphorylated Smad-3 and phosphorylated transforming growth factor　β type 1 receptor in CFs. TIMP-1, -3, and -4 also inhibited the FAK, AKT, and ERK pathways that induce cardiac hypertrophy. Collagen gels containing TIMP-1 or TIMP-3 were transplanted to the left ventricular anterior wall of an ischemic cardiomyopathy(ICM) rat. Gel-released TIMP-1 and TIMP-3 significantly improved cardiac function and myocardial remodeling and enhanced SMA expression in the infarcted area in ICM rat. TIMPs may be an ideal target of cardiac regeneration therapy.

Free Research Field

心臓血管病理学