Cardiac-specific mindin overexpression attenuates cardiac hypertrophy via blocking AKT/GSK3β and TGF-β1Smad signalling

Ling Yan, Xiang Wei, Qi Zhu Tang, Jinghua Feng, Yan Zhang, Chen Liu, Zhou Yan Bian, Lian Feng Zhang, Manyin Chen, Xue Bai, Ai Bing Wang, John Fassett, Yingjie Chen, You Wen He, Qinglin Yang, Peter P. Liu, Hongliang Li

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66 Scopus citations


Aims Mindin is a secreted extracellular matrix protein, an integrin ligand, and an angiogenesis inhibitor, other examples of which are all key players in the progression of cardiac hypertrophy. However, its function during cardiac hypertrophy remains unclear. This study was aimed to identify the effect of mindin on cardiac hypertrophy and the underlying mechanisms. Methods and resultsA significant down-regulation of mindin expression was observed in human failing hearts. To further investigate the role of mindin in cardiac hypertrophy, we used cultured neonatal rat cardiomyocytes with gain and loss of mindin function and cardiac-specific Mindin-overexpressing transgenic (TG) mice. In cultured cardiomyocytes, mindin negatively regulated angiotensin II (Ang II)-mediated hypertrophic growth, as detected by [ 3H]-Leucine incorporation, cardiac myocyte area, and hypertrophic marker protein levels. Cardiac hypertrophy in vivo was produced by aortic banding (AB) or Ang II infusion in TG mice and their wild-type controls. The extent of cardiac hypertrophy was evaluated by echocardiography as well as by pathological and molecular analyses of heart samples. Mindin overexpression in the heart markedly attenuated cardiac hypertrophy, fibrosis, and left ventricular dysfunction in mice in response to AB or Ang II. Further analysis of the signalling events in vitro and in vivo indicated that these beneficial effects of mindin were associated with the interruption of AKT/glycogen synthase kinase 3β (GSK3β) and transforming growth factor (TGF)-β1Smad signalling. ConclusionThe present study demonstrates for the first time that mindin serves as a novel mediator that protects against cardiac hypertrophy and the transition to heart failure by blocking AKT/GSK3β and TGF-β1Smad signalling.

Original languageEnglish (US)
Pages (from-to)85-94
Number of pages10
JournalCardiovascular Research
Issue number1
StatePublished - Oct 1 2011

Bibliographical note

Funding Information:
This work was supported by the National Natural Science Foundation of China (30900524, 30972954, 81000036, and 81000095), the Support Program for Disciplinary Leaders in Wuhan (200951830561), the Fundamental Research Funds for the Central Universities (3081013), and the National Basic Research Program of China (2011CB503902).


  • AKT
  • Hypertrophy
  • Mindin
  • Remodelling
  • Signal transduction


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