Copyright © 2007, European Society of Cardiology
Adiponectin accumulates in myocardial tissue that has been damaged by ischemia-reperfusion injury via leakage from the vascular compartment
aMolecular Cardiology/Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany Street, W611, Boston, MA 02118, USA
bDepartment of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2, Yamada-oka, Suita, Osaka, 565-0871, Japan
* Corresponding author. Tel.: +1 617 414 2390; fax: +1 617 414 2391. Email address: kxwalsh{at}bu.edu
Objectives: Adiponectin, a circulating adipocyte-derived hormone, exerts beneficial actions on hearts subjected to ischemia-reperfusion injury. Adiponectin exists in plasma as three different oligomeric forms: trimer, hexamer and high molecular weight. This study investigated the expression and myocardial accumulation of adiponectin in a murine model of ischemia-reperfusion injury.
Methods: Wild-type and adiponectin deficient mice were subjected to left anterior descending artery ligation followed by reperfusion. Plasma adiponectin levels were analyzed by ELISA and adiponectin in heart was determined by immunohistochemical, Western blot and real-time PCR analyses.
Results: Plasma adiponectin levels declined after myocardial ischemia-reperfusion injury due to reductions in high molecular weight and, to a lesser extent, trimer and hexamer isoforms. Adiponectin protein was detected in injured but not sham-operated heart, and this was accompanied by a negligible increase in adiponectin transcript in the myocardium. Systemic delivery of adiponectin to adiponectin knockout (APN-KO) mice led to the accumulation of adiponectin in ischemia-reperfusion-injured, but not-uninjured hearts at levels comparable to wild-type suggesting that cardiac expression of adiponectin does not appreciably contribute to its accumulation in the infarcted heart. The serum half-life of adiponectin was 7.4±0.3 h in ischemia-reperfusion and 9.7±0.5 h in sham-operated mice (P>0.05), whereas the half-life of adiponectin in the damaged heart was 26.9±2.2 h (P<0.05).
Conclusions: These data show that adiponectin accumulates in the heart following ischemic damage primarily through leakage from the vascular compartment, and that adiponectin has a longer half-life in damaged heart tissue than in plasma.
KEYWORDS Adiponectin; Ischemia-reperfusion; Myocardium; Infarction
Abbreviations: AAR, area at risk • APN, adiponectin • CAD, coronary artery disease • HMW, high molecular weight • IA, infarct area • I-R, ischemia-reperfusion injury • KO, knockout • LAD, left anterior descending artery • LV, left ventricular • WAT, white adipose tissue.
Time for primary review 31 days
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