Tissue Inhibitor of Metalloproteinase-1 and -3 Improves Cardiac Function in an Ischemic Cardiomyopathy Model Rat

被引：0

作者：

Uchinaka, Ayako ^{[1
]}

Kawaguchi, Naomasa ^{[1
,2
]}

Mori, Seiji ^{[1
]}

Hamada, Yoshinosuke ^{[1
]}

Miyagawa, Shigeru ^{[3
]}

Saito, Atsuhiro ^{[4
]}

Sawa, Yoshiki ^{[3
]}

Matsuura, Nariaki ^{[1
]}

机构：

[1] Osaka Univ, Grad Sch Med, Dept Mol Pathol, Div Hlth Sci, Suita, Osaka 5650871, Japan

[2] Osaka Univ, Grad Sch Med, Dept Cardiovasc Pathol, Div Hlth Sci, Suita, Osaka 5650871, Japan

[3] Osaka Univ, Grad Sch Med, Dept Cardiovasc Surg, Suita, Osaka 5650871, Japan

[4] Osaka Univ, Grad Sch Med, Osaka Univ Hosp, Med Ctr Translat Res, Suita, Osaka 5650871, Japan

来源：

TISSUE ENGINEERING PART A | 2014年 / 20卷 / 21-22期

关键词：

FOCAL ADHESION KINASE; II TYPE-2 RECEPTOR; MYOCARDIAL-INFARCTION; MATRIX METALLOPROTEINASES; DILATED CARDIOMYOPATHY; CONTRACTILE ACTIVITY; HEART-FAILURE; EXPRESSION; TIMP-3; MICE;

D O I：

10.1089/ten.tea.2013.0763

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Matrix metalloproteinases (MMPs) and a family of tissue inhibitors of metalloproteinases (TIMPs) may contribute to myocardial remodeling in heart failure. TIMPs are the main inhibitors of MMPs and have other MMP-independent functions. Because little is known of the role of TIMPs in the heart, we examined the effects of TIMPs on cardiac fibroblasts (CFs) and cardiomyocytes. 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 (TGF)-beta type 1 receptor in CFs; this effect was inhibited by TGF-beta receptor blocker SB-505124. TIMPs-1, -3, and -4 also inhibited the FAK, AKT, and ERK pathways that induce cardiac hypertrophy. TIMP-1 and TIMP-2 suppressed apoptosis in cardiomyocytes; in contrast, TIMP-4 induced apoptosis in CFs. TIMP-2 stimulated collagen synthesis. Collagen gels containing TIMP-1 or TIMP-3, which exhibit cardioprotective effects in vitro, were transplanted to the left ventricular anterior wall of a rat heart model of myocardial infarction. Gel-released TIMP-1 and TIMP-3 significantly improved cardiac function and myocardial remodeling and enhanced SMA expression in the infarcted area in ischemic cardiomyopathy model rats. Further, the transplantation of TIMP-1 or TIMP-3 gels inhibited apoptosis in the ischemic myocardium and reduced MMP-2 activity. TIMPs may be an ideal target of cardiac regeneration therapy.

引用

页码：3073 / 3084

页数：12