Inhibition of p38 alpha MAPK rescues cardiomyopathy induced by overexpressed beta 2-adrenergic receptor, but not beta 1-adrenergic receptor.

Journal Article (Journal Article)

We examined the role of p38alpha MAPK in mediating cardiomyopathy in mice overexpressing beta(1)-adrenergic receptor (beta(1)-AR) or beta(2)-AR by mating them with dominant-negative p38alpha (DNp38alpha) MAPK mice. Both beta(1)-AR and beta(2)-AR Tg mice had enhanced LV ejection fraction (LVEF) as young adults and developed similar cardiomyopathy at 11-15 months, characterized by reduced LVEF, myocyte hypertrophy, fibrosis, and apoptosis. We inhibited p38alpha MAPK by mating beta(1)-AR Tg and beta(2)-AR Tg mice with DNp38alpha MAPK mice, which rescued the depressed LVEF and reduced apoptosis and fibrosis in bigenic beta(2)-AR x DNp38alpha MAPK mice, but not bigenic beta(1)-AR x DNp38alpha MAPK mice, and failed to reduce myocyte hypertrophy in either group. G(salpha) was increased in both beta(1)-AR Tg and beta(2)-AR Tg mice and was still present in bigenic beta(1)-AR x DNp38alpha MAPK mice, but not bigenic beta(2)-AR x DNp38alpha MAPK mice. This suggests that p38alpha MAPK is one critical downstream signal for the development of cardiomyopathy following chronic beta(2)-AR stimulation, but other kinases may be more important in ameliorating the adverse effects of chronic beta(1)-AR stimulation.

Full Text

Duke Authors

Cited Authors

  • Peter, PS; Brady, JE; Yan, L; Chen, W; Engelhardt, S; Wang, Y; Sadoshima, J; Vatner, SF; Vatner, DE

Published Date

  • May 2007

Published In

Volume / Issue

  • 117 / 5

Start / End Page

  • 1335 - 1343

PubMed ID

  • 17446930

Pubmed Central ID

  • PMC1849986

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/JCI29576

Language

  • eng

Conference Location

  • United States