Nature Medicine 11, 1096 - 1103 (2005)
Published online: 11 September 2005; | doi:10.1038/nm1295
Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2−dependent mechanismsRei Shibata1, Kaori Sato1, David R Pimentel2, Yukihiro Takemura1, Shinji Kihara3, Koji Ohashi3, Tohru Funahashi3, Noriyuki Ouchi1
& Kenneth Walsh11
Molecular Cardiology/Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany Street, Boston, Massachusetts 02118, USA. 2
Cardiovascular Medicine Section, Department of Medicine, Boston University Medical Center, and Myocardial Biology Unit, Boston University School of Medicine, 715 Albany Street, Boston, Massachusetts 02118, USA. 3
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, 2-2, Yamada-oka, Suita, Osaka, 565-0871, Japan.
Correspondence should be addressed to Kenneth Walsh kxwalsh@bu.edu or Noriyuki Ouchi nouchi@bu.edu Obesity-related disorders are associated with the development of ischemic heart disease. Adiponectin is a circulating adipose-derived cytokine that is downregulated in obese individuals and after myocardial infarction. Here, we examine the role of adiponectin in myocardial remodeling in response to acute injury. Ischemia-reperfusion in adiponectin-deficient (APN-KO) mice resulted in increased myocardial infarct size, myocardial apoptosis and tumor necrosis factor (TNF)- expression compared with wild-type mice. Administration of adiponectin diminished infarct size, apoptosis and TNF- production in both APN-KO and wild-type mice. In cultured cardiac cells, adiponectin inhibited apoptosis and TNF- production. Dominant negative AMP-activated protein kinase (AMPK) reversed the inhibitory effects of adiponectin on apoptosis but had no effect on the suppressive effect of adiponectin on TNF- production. Adiponectin induced cyclooxygenase (COX)-2−dependent synthesis of prostaglandin E2 in cardiac cells, and COX-2 inhibition reversed the inhibitory effects of adiponectin on TNF- production and infarct size. These data suggest that adiponectin protects the heart from ischemia-reperfusion injury through both AMPK- and COX-2−dependent mechanisms.
MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated.
|
