Disruption of mindin exacerbates cardiac hypertrophy and fibrosis

被引:31
作者
Bian, Zhou-Yan [1 ,2 ]
Wei, Xiang [3 ]
Deng, Shan [4 ]
Tang, Qi-Zhu [1 ,2 ]
Feng, Jinghua [1 ,2 ]
Zhang, Yan [1 ,2 ]
Liu, Chen [5 ]
Jiang, Ding-Sheng [1 ,2 ]
Yan, Ling [1 ,2 ]
Zhang, Lian-Feng [6 ]
Chen, Manyin [7 ]
Fassett, John [8 ]
Chen, Yingjie [8 ]
He, You-Wen [9 ]
Yang, Qinglin [10 ]
Liu, Peter P. [7 ]
Li, Hongliang [1 ,2 ]
机构
[1] Wuhan Univ, Cardiovasc Res Inst, Wuhan 430060, Peoples R China
[2] Wuhan Univ, Dept Cardiol, Renmin Hosp, Wuhan 430060, Peoples R China
[3] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Thorac & Cardiovasc Surg, Wuhan 430030, Peoples R China
[4] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Cardiol,Inst Cardiovasc Dis, Wuhan 430030, Peoples R China
[5] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Cardiol, Guangzhou 510275, Guangdong, Peoples R China
[6] Minist Hlth, Key Lab Human Dis Comparat Med, Beijing, Peoples R China
[7] Univ Toronto, Univ Hlth Network, Div Cardiol Heart & Stroke, Richard Lewar Ctr Excellence, Toronto, ON M5S 3E2, Canada
[8] Univ Minnesota, Div Cardiovasc, Minneapolis, MN 55455 USA
[9] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA
[10] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA
来源
JOURNAL OF MOLECULAR MEDICINE-JMM | 2012年 / 90卷 / 08期
基金
中国国家自然科学基金;
关键词
Mindin; Hypertrophy; Remodelling; Signal transduction; AKT; MATRIX PROTEIN MINDIN; OVEREXPRESSION; GROWTH; AKT; ANGIOGENESIS; SPONDIN; KINASE;
D O I
10.1007/s00109-012-0883-2
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Cardiac hypertrophy is a response of the myocardium to increased workload and is characterised by an increase of myocardial mass and an accumulation of extracellular matrix (ECM). As an ECM protein, an integrin ligand, and an angiogenesis inhibitor, all of which are key players in cardiac hypertrophy, mindin is an attractive target for therapeutic intervention to treat or prevent cardiac hypertrophy and heart failure. In this study, we investigated the role of mindin in cardiac hypertrophy using littermate Mindin knockout (Mindin (-/-) ) and wild-type (WT) mice. Cardiac hypertrophy was induced by aortic banding (AB) or angiotensin II (Ang II) infusion in Mindin (-/-) and WT mice. The extent of cardiac hypertrophy was quantitated by echocardiography and by pathological and molecular analyses of heart samples. Mindin (-/-) mice were more susceptible to cardiac hypertrophy and fibrosis in response to AB or Ang II stimulation than wild type. Cardiac function was also markedly exacerbated during both systole and diastole in Mindin (-/-) mice in response to hypertrophic stimuli. Western blot assays further showed that the activation of AKT/glycogen synthase kinase 3 beta (GSK3 beta) signalling in response to hypertrophic stimuli was significantly increased in Mindin (-/-) mice. Moreover, blocking AKT/GSK3 beta signalling with a pharmacological AKT inhibitor reversed cardiac abnormalities in Mindin (-/-) mice. Our data show that mindin, as an intrinsic cardioprotective factor, prevents maladaptive remodelling and the transition to heart failure by blocking AKT/GSK3 beta signalling.
引用
收藏
页码:895 / 910
页数:16
相关论文
共 28 条
[1]   ECM remodeling in hypertensive heart disease [J].
Berk, Bradford C. ;
Fujiwara, Keigi ;
Lehoux, Stephanie .
JOURNAL OF CLINICAL INVESTIGATION, 2007, 117 (03) :568-575
[2]   LIM and Cysteine-Rich Domains 1 Regulates Cardiac Hypertrophy by Targeting Calcineurin/Nuclear Factor of Activated T Cells Signaling [J].
Bian, Zhou-Yan ;
Huang, He ;
Jiang, Hong ;
Shen, Di-Fei ;
Yan, Ling ;
Zhu, Li-Hua ;
Wang, Lang ;
Cao, Feng ;
Liu, Chen ;
Tang, Qi-Zhu ;
Li, Hongliang .
HYPERTENSION, 2010, 55 (02) :257-U108
[3]   Melusin, a muscle-specific integrin β1-interacting protein, is required to prevent cardiac failure in response to chronic pressure overload [J].
Brancaccio, M ;
Fratta, L ;
Notte, A ;
Hirsch, E ;
Poulet, R ;
Guazzone, S ;
De Acetis, M ;
Vecchione, C ;
Marino, G ;
Altruda, F ;
Silengo, L ;
Tarone, G ;
Lembo, G .
NATURE MEDICINE, 2003, 9 (01) :68-75
[4]   Crocetin protects against cardiac hypertrophy by blocking MEK-ERK1/2 signalling pathway [J].
Cai, Jun ;
Yi, Fang-Fang ;
Bian, Zhou-Yan ;
Shen, Di-Fei ;
Yang, Long ;
Yan, Ling ;
Tang, Qi-Zhu ;
Yang, Xin-Chun ;
Li, Hongliang .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2009, 13 (05) :909-925
[5]   AKT signalling in the failing heart [J].
Chaanine, Antoine H. ;
Hajjar, Roger J. .
EUROPEAN JOURNAL OF HEART FAILURE, 2011, 13 (08) :825-829
[6]   Gene expression changes associated with fibronectin-induced cardiac myocyte hypertrophy [J].
Chen, H ;
Huang, XYN ;
Stewart, AFR ;
Sepulveda, JL .
PHYSIOLOGICAL GENOMICS, 2004, 18 (03) :273-283
[7]   Akt induces enhanced myocardial contractility and cell size in vivo in transgenic mice [J].
Condorelli, G ;
Drusco, A ;
Stassi, G ;
Bellacosa, A ;
Roncarati, R ;
Iaccarino, G ;
Russo, MA ;
Gu, YS ;
Dalton, N ;
Chung, C ;
Latronico, MVG ;
Napoli, C ;
Sadoshima, J ;
Croce, CM ;
Ross, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (19) :12333-12338
[8]   The neuronal class 2 TSR proteins F-spondin and Mindin: a small family with divergent biological activities [J].
Feinstein, Y ;
Klar, A .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2004, 36 (06) :975-980
[9]   The extracellular matrix protein mindin is a pattern-recognition molecule for microbial pathogens [J].
He, YW ;
Li, H ;
Zhang, J ;
Hsu, CL ;
Lin, E ;
Zhang, N ;
Guo, J ;
Forbush, KA ;
Bevan, MJ .
NATURE IMMUNOLOGY, 2004, 5 (01) :88-97
[10]   Regulation of cardiac hypertrophy by intracellular signalling pathways [J].
Heineke, Joerg ;
Molkentin, Jeffery D. .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2006, 7 (08) :589-600