Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2-dependent mechanisms

Nat Med. 2005 Oct;11(10):1096-103. doi: 10.1038/nm1295. Epub 2005 Sep 11.

Abstract

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)-alpha expression compared with wild-type mice. Administration of adiponectin diminished infarct size, apoptosis and TNF-alpha production in both APN-KO and wild-type mice. In cultured cardiac cells, adiponectin inhibited apoptosis and TNF-alpha 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-alpha production. Adiponectin induced cyclooxygenase (COX)-2-dependent synthesis of prostaglandin E(2) in cardiac cells, and COX-2 inhibition reversed the inhibitory effects of adiponectin on TNF-alpha production and infarct size. These data suggest that adiponectin protects the heart from ischemia-reperfusion injury through both AMPK- and COX-2-dependent mechanisms.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AMP-Activated Protein Kinases
  • Adiponectin / pharmacology*
  • Animals
  • Apoptosis / drug effects
  • Cells, Cultured
  • Cyclooxygenase 2 / metabolism*
  • Cyclooxygenase Inhibitors / pharmacology
  • Cytoprotection / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Multienzyme Complexes / metabolism*
  • Muscle Cells / drug effects
  • Muscle Cells / pathology
  • Myocardial Ischemia / enzymology
  • Myocardial Ischemia / pathology
  • Myocardial Ischemia / prevention & control*
  • Myocardial Reperfusion Injury / enzymology
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Nitrobenzenes / pharmacology
  • Protein-Serine-Threonine Kinases / metabolism*
  • Rats
  • Signal Transduction
  • Sulfonamides / pharmacology
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Adiponectin
  • Cyclooxygenase Inhibitors
  • Multienzyme Complexes
  • Nitrobenzenes
  • Sulfonamides
  • Tumor Necrosis Factor-alpha
  • N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
  • Cyclooxygenase 2
  • Protein-Serine-Threonine Kinases
  • AMP-Activated Protein Kinases