T-cadherin is critical for adiponectin-mediated cardioprotection in mice

被引:293
作者
Denzel, Martin S. [1 ]
Scimia, Maria-Cecilia [1 ,2 ]
Zumstein, Philine M. [1 ]
Walsh, Kenneth [3 ]
Ruiz-Lozano, Pilar [1 ]
Ranscht, Barbara [1 ]
机构
[1] Sanford Burnham Med Res Inst, La Jolla, CA 92037 USA
[2] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA
[3] Boston Univ, Sch Med, Mol Cardiol CVI, Boston, MA 02118 USA
关键词
LEFT-VENTRICULAR HYPERTROPHY; INDUCED INSULIN-RESISTANCE; MYOCARDIAL-INFARCTION; CARDIAC DYSFUNCTION; PLASMA ADIPONECTIN; PRESSURE-OVERLOAD; DEFICIENCY; PROTEIN; HYPOADIPONECTINEMIA; ASSOCIATION;
D O I
10.1172/JCI43464
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The circulating, adipocyte-secreted hormone adiponectin (APN) exerts protective effects on the heart under stress conditions. The receptors binding APN to cardiac tissue, however, have remained elusive. Here, we report that the glycosyl phosphatidylinositol-anchored cell surface glycoprotein T-cadherin (encoded by Cdh13) protects against cardiac stress through its association with APN in mice. We observed extensive colocalization of T-cadherin and APN on cardiomyocytes in vivo. In T-cadherin-deficient mice, APN failed to associate with cardiac tissue, and its levels dramatically increased in the circulation. Pressure overload stress resulted in exacerbated cardiac hypertrophy in T-cadherin-null mice and paralleled corresponding defects in mice lacking APN. During ischemia-reperfusion injury, the absence of T-cadherin increased infarct size similar to that in APN-null mice. Myocardial AMPK is a major downstream protective signaling target of APN. In both cardiac hypertrophy and ischemia-reperfusion models, T-cadherin was necessary for APN-dependent AMPK phosphorylation. In APN-null mice, recombinant adenovirus-expressed APN reduced exaggerated hypertrophy and infarct size and restored AMPK phosphorylation as previously reported. In contrast, rescue was ineffective in mice lacking T-cadherin in addition to APN. These data suggest that T-cadherin protects from stressinduced pathological cardiac remodeling by binding APN and activating its cardioprotective functions.
引用
收藏
页码:4342 / 4352
页数:11
相关论文
共 52 条
[1]   Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity [J].
Arita, Y ;
Kihara, S ;
Ouchi, N ;
Takahashi, M ;
Maeda, K ;
Miyagawa, J ;
Hotta, K ;
Shimomura, I ;
Nakamura, T ;
Miyaoka, K ;
Kuriyama, H ;
Nishida, M ;
Yamashita, S ;
Okubo, K ;
Matsubara, K ;
Muraguchi, M ;
Ohmoto, Y ;
Funahashi, T ;
Matsuzawa, Y .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1999, 257 (01) :79-83
[2]   Clinical Impact of Left Ventricular Hypertrophy and Implications for Regression [J].
Artham, Surya M. ;
Lavie, Carl J. ;
Milani, Richard V. ;
Patel, Dharmendrakumar A. ;
Verma, Anil ;
Ventura, Hector O. .
PROGRESS IN CARDIOVASCULAR DISEASES, 2009, 52 (02) :153-167
[3]   Opposing effects of adiponectin receptors 1 and 2 on energy metabolism [J].
Bjursell, Mikael ;
Ahnmark, Andrea ;
Bohlooly-Y, Mohammad ;
William-Olsson, Lena ;
Rhedin, Magdalena ;
Peng, Xiao-Rong ;
Ploj, Karolina ;
Gerdin, Anna-Karin ;
Arnerup, Gunnel ;
Elmgren, Anders ;
Berg, Anna-Lena ;
Oscarsson, Jan ;
Linden, Daniel .
DIABETES, 2007, 56 (03) :583-593
[4]   Hypoadiponectinemia is associated with ischemic cerebrovascular disease [J].
Chen, MP ;
Tsai, JCR ;
Chung, FM ;
Yang, SS ;
Hsing, LL ;
Shin, SJ ;
Lee, YJ .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2005, 25 (04) :821-826
[5]   T-cadherin structures reveal a novel adhesive binding mechanism [J].
Ciatto, Carlo ;
Bahna, Fabiana ;
Zampieri, Niccolo ;
VanSteenhouse, Harper C. ;
Katsamba, Phini S. ;
Ahlsen, Goran ;
Harrison, Oliver J. ;
Brasch, Julia ;
Jin, Xiangshu ;
Posy, Shoshana ;
Vendome, Jeremie ;
Ranscht, Barbara ;
Jessell, Thomas M. ;
Honig, Barry ;
Shapiro, Lawrence .
NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2010, 17 (03) :339-U110
[6]   Integrin binding angiopoietin-1 monomers reduce cardiac hypertrophy [J].
Dallabrida, Susan M. ;
Ismail, Nesreen S. ;
Pravda, Elke A. ;
Parodi, Emily M. ;
Dickie, Renee ;
Durand, Ellen M. ;
Lai, Jean ;
Cassiola, Flavia ;
Rogers, Rick A. ;
Rupnick, Maria A. .
FASEB JOURNAL, 2008, 22 (08) :3010-3023
[7]   Adiponectin Deficiency Limits Tumor Vascularization in the MMTV-PyV-mT Mouse Model of Mammary Cancer [J].
Denzel, Martin S. ;
Hebbard, Lionel W. ;
Shostak, Gregory ;
Shapiro, Lawrence ;
Cardiff, Robert D. ;
Ranscht, Barbara .
CLINICAL CANCER RESEARCH, 2009, 15 (10) :3256-3264
[8]   T-cadherin is a major glycophosphoinositol-anchored protein associated with noncaveolar detergent-insoluble domains of the cardiac sarcolemma [J].
Doyle, DD ;
Goings, GE ;
Upshaw-Earley, J ;
Page, E ;
Ranscht, B ;
Palfrey, HC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (12) :6937-6943
[9]   Primary care: Cardiac resuscitation [J].
Eisenberg, MS ;
Mengert, TJ .
NEW ENGLAND JOURNAL OF MEDICINE, 2001, 344 (17) :1304-1313
[10]  
FREDETTE BJ, 1994, J NEUROSCI, V14, P7331