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Cardiac-specific mindin overexpression attenuates cardiac hypertrophy via blocking AKT/GSK3β and TGF-β1-Smad signalling.

Publication ,  Journal Article
Yan, L; Wei, X; Tang, Q-Z; Feng, J; Zhang, Y; Liu, C; Bian, Z-Y; Zhang, L-F; Chen, M; Bai, X; Wang, A-B; Fassett, J; Chen, Y; He, Y-W ...
Published in: Cardiovasc Res
October 1, 2011

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 RESULTS: A 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 [(3)H]-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)-β1-Smad signalling. CONCLUSION: The 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-β1-Smad signalling.

Duke Scholars

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Published In

Cardiovasc Res

DOI

EISSN

1755-3245

Publication Date

October 1, 2011

Volume

92

Issue

1

Start / End Page

85 / 94

Location

England

Related Subject Headings

  • Transforming Growth Factor beta1
  • TOR Serine-Threonine Kinases
  • Smad Proteins
  • Signal Transduction
  • Rats, Sprague-Dawley
  • Rats
  • Proto-Oncogene Proteins c-akt
  • Phosphorylation
  • Myocardium
  • Mice, Inbred C57BL
 

Citation

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Yan, L., Wei, X., Tang, Q.-Z., Feng, J., Zhang, Y., Liu, C., … Li, H. (2011). Cardiac-specific mindin overexpression attenuates cardiac hypertrophy via blocking AKT/GSK3β and TGF-β1-Smad signalling. Cardiovasc Res, 92(1), 85–94. https://doi.org/10.1093/cvr/cvr159
Yan, Ling, Xiang Wei, Qi-Zhu Tang, Jinghua Feng, Yan Zhang, Chen Liu, Zhou-Yan Bian, et al. “Cardiac-specific mindin overexpression attenuates cardiac hypertrophy via blocking AKT/GSK3β and TGF-β1-Smad signalling.Cardiovasc Res 92, no. 1 (October 1, 2011): 85–94. https://doi.org/10.1093/cvr/cvr159.
Yan L, Wei X, Tang Q-Z, Feng J, Zhang Y, Liu C, et al. Cardiac-specific mindin overexpression attenuates cardiac hypertrophy via blocking AKT/GSK3β and TGF-β1-Smad signalling. Cardiovasc Res. 2011 Oct 1;92(1):85–94.
Yan, Ling, et al. “Cardiac-specific mindin overexpression attenuates cardiac hypertrophy via blocking AKT/GSK3β and TGF-β1-Smad signalling.Cardiovasc Res, vol. 92, no. 1, Oct. 2011, pp. 85–94. Pubmed, doi:10.1093/cvr/cvr159.
Yan L, Wei X, Tang Q-Z, Feng J, Zhang Y, Liu C, Bian Z-Y, Zhang L-F, Chen M, Bai X, Wang A-B, Fassett J, Chen Y, He Y-W, Yang Q, Liu PP, Li H. Cardiac-specific mindin overexpression attenuates cardiac hypertrophy via blocking AKT/GSK3β and TGF-β1-Smad signalling. Cardiovasc Res. 2011 Oct 1;92(1):85–94.
Journal cover image

Published In

Cardiovasc Res

DOI

EISSN

1755-3245

Publication Date

October 1, 2011

Volume

92

Issue

1

Start / End Page

85 / 94

Location

England

Related Subject Headings

  • Transforming Growth Factor beta1
  • TOR Serine-Threonine Kinases
  • Smad Proteins
  • Signal Transduction
  • Rats, Sprague-Dawley
  • Rats
  • Proto-Oncogene Proteins c-akt
  • Phosphorylation
  • Myocardium
  • Mice, Inbred C57BL