on February 28, 2008
Published online before print February 28, 2008, doi: 10.1161/ATVBAHA.107.156687
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on September 25, 2007
Accepted on February 15, 2008
Adiponectin Protects Against Angiotensin II–Induced Cardiac Fibrosis Through Activation of PPARalpha
Koichi Fujita ;
From the Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Japan.
* To whom correspondence should be addressed. E-mail: nmaeda{at}imed2.med.osaka-u.ac.jp.
Objectives—Adiponectin is recognized as an antidiabetic, antiatherosclerotic, and antiinflammatory protein derived from adipocytes. However, the role of adiponectin in cardiac fibrosis remains uncertain. We herein explore the effects of adiponectin on cardiac fibrosis induced by angiotensin II (Ang II).
Methods and Results—Wild-type (WT), adiponectin knockout (Adipo-KO), and PPAR
knockout (PPAR-KO) mice were infused with Ang II at 1.2 mg/kg/d. Severe cardiac fibrosis and left ventricular dysfunction were observed in Ang II–infused Adipo-KO mice compared to WT mice. Adenovirus-mediated adiponectin treatment improved the above phenotypes and the dysregulation of reactive oxygen species (ROS)-related mRNAs in Adipo-KO mice, whereas such amelioration was not observed in PPAR-KO mice despite adiponectin accumulation in heart tissue. In cultured cardiac fibroblasts, adiponectin improved the reduction of AMP-activated protein kinase (AMPK) activity and elevation of extracellular signal–regulated kinase 1/2 (ERK1/2) activity induced by Ang II. Adiponectin significantly enhanced PPAR activity, whereas the adiponectin-dependent PPAR activation was diminished by Compound C, an inhibitor of AMPK.
Conclusion—The present study suggests that adiponectin protects against Ang II–induced cardiac fibrosis possibly through AMPK-dependent PPAR activation.
Key words: adiponectin • angiotensin II • PPAR
•
fibrosis •
AMPK
This article has been cited by other articles:
 |
|
 |
|
  A. Kis, C. Murdoch, M. Zhang, A. Siva, S. Rodriguez-Cuenca, S. Carobbio, A. Lukasik, M. Blount, S. O'Rahilly, S. L. Gray, et al. Defective peroxisomal proliferators activated receptor gamma activity due to dominant-negative mutation synergizes with hypertension to accelerate cardiac fibrosis in mice Eur J Heart Fail, June 1, 2009; 11(6): 533 - 541. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Krenning, J.-R. A.J. Moonen, and M. C. Harmsen Pleiotropism of Adiponectin: Inflammation, Neovascularization, and Fibrosis Circ. Res., May 8, 2009; 104(9): 1029 - 1031. [Full Text] [PDF]
|
|
|
|
 |
|
 D. Huang, C. Yang, Y. Wang, Y. Liao, and K. Huang PARP-1 suppresses adiponectin expression through poly(ADP-ribosyl)ation of PPAR{gamma} in cardiac fibroblasts Cardiovasc Res, January 1, 2009; 81(1): 98 - 107. [Abstract] [Full Text] [PDF]
|
|