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Role of p38alpha MAPK in cardiac apoptosis and remodeling after myocardial infarction.

Publication ,  Journal Article
Ren, J; Zhang, S; Kovacs, A; Wang, Y; Muslin, AJ
Published in: J Mol Cell Cardiol
April 2005

Acute coronary occlusion results in ischemia-mediated death of cardiomyocytes. In the days and weeks following myocardial infarction (MI), left ventricular remodeling occurs that is characterized by persistent cardiomyocyte apoptosis, thinning and fibrosis at the site of infarction, ventricular chamber dilatation, and growth of remaining viable cardiomyocytes. The p38 mitogen-activated protein kinase (MAPK) signaling cascade has been implicated in the remodeling process. In this work, mice with cardiac-specific expression of a dominant negative mutant form of p38 MAPK (DN-p38alpha) were subjected to MI by occlusion of the left coronary artery. Acute ischemia area was determined by transthoracic echocardiography 2 h after MI surgery, and was found to be nearly identical in DN-p38 mice and their wild-type littermates. Seven days after MI, mice were subjected to repeat echocardiography and histological examination of infarct size. DN-p38 mice had markedly reduced infarct size and increased ventricular systolic function 7 days after MI when compared to wild-type littermates. In addition, DN-p38 mice had less cardiomyocyte apoptosis than wild-type mice in the infarct border zone. Recently, it was discovered that Bcl-X(L) deamidation occurs in vivo, and this results in Bcl-X(L) degradation that sensitizes cells to apoptosis by enhancing BAX activity. Bcl-X(L) deamidation was found to occur in the cardiac tissue of wild-type mice after MI, but was reduced in DN-p38 mice. These results establish that p38 MAPK activity is required for pathological remodeling after MI and suggest that p38 MAPK may promote cardiomyocyte apoptosis through Bcl-X(L) deamidation.

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Published In

J Mol Cell Cardiol

DOI

ISSN

0022-2828

Publication Date

April 2005

Volume

38

Issue

4

Start / End Page

617 / 623

Location

England

Related Subject Headings

  • bcl-X Protein
  • Ventricular Remodeling
  • Proto-Oncogene Proteins c-bcl-2
  • Myocytes, Cardiac
  • Myocardial Infarction
  • Mutation
  • Mitogen-Activated Protein Kinase 14
  • Mice, Transgenic
  • Mice
  • Cardiovascular System & Hematology
 

Citation

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Ren, J., Zhang, S., Kovacs, A., Wang, Y., & Muslin, A. J. (2005). Role of p38alpha MAPK in cardiac apoptosis and remodeling after myocardial infarction. J Mol Cell Cardiol, 38(4), 617–623. https://doi.org/10.1016/j.yjmcc.2005.01.012
Ren, Jie, Shaosong Zhang, Attila Kovacs, Yibin Wang, and Anthony J. Muslin. “Role of p38alpha MAPK in cardiac apoptosis and remodeling after myocardial infarction.J Mol Cell Cardiol 38, no. 4 (April 2005): 617–23. https://doi.org/10.1016/j.yjmcc.2005.01.012.
Ren J, Zhang S, Kovacs A, Wang Y, Muslin AJ. Role of p38alpha MAPK in cardiac apoptosis and remodeling after myocardial infarction. J Mol Cell Cardiol. 2005 Apr;38(4):617–23.
Ren, Jie, et al. “Role of p38alpha MAPK in cardiac apoptosis and remodeling after myocardial infarction.J Mol Cell Cardiol, vol. 38, no. 4, Apr. 2005, pp. 617–23. Pubmed, doi:10.1016/j.yjmcc.2005.01.012.
Ren J, Zhang S, Kovacs A, Wang Y, Muslin AJ. Role of p38alpha MAPK in cardiac apoptosis and remodeling after myocardial infarction. J Mol Cell Cardiol. 2005 Apr;38(4):617–623.
Journal cover image

Published In

J Mol Cell Cardiol

DOI

ISSN

0022-2828

Publication Date

April 2005

Volume

38

Issue

4

Start / End Page

617 / 623

Location

England

Related Subject Headings

  • bcl-X Protein
  • Ventricular Remodeling
  • Proto-Oncogene Proteins c-bcl-2
  • Myocytes, Cardiac
  • Myocardial Infarction
  • Mutation
  • Mitogen-Activated Protein Kinase 14
  • Mice, Transgenic
  • Mice
  • Cardiovascular System & Hematology