Adiponectin protects against myocardial ischaemia-reperfusion injury via AMP-activated protein kinase, Akt, and nitric oxide.

Abstract

AIMS:

Cardiovascular disease and type 2 diabetes mellitus are associated with low plasma concentration of adiponectin. The aim of this study was to investigate whether adiponectin exerts cardioprotective effects during myocardial ischaemia-reperfusion and whether this effect is related to the production of nitric oxide (NO).

METHODS AND RESULTS:

Isolated rat hearts were subjected to 30 min of either global or local ischaemia followed by 60 min of reperfusion. The hearts received vehicle, adiponectin (3 microg/mL), the NO-synthase inhibitor nitro-l-arginine (L-NNA) (0.1 mM), or a combination of adiponectin and L-NNA at the onset of ischaemia. Haemodynamics, infarct size, and expression of endothelial NO-synthase (eNOS), AMP-activated protein kinase (AMPK), and Akt were determined. Adiponectin significantly increased left ventricular function and coronary flow during reperfusion in comparison with the vehicle group. Co-administration of L-NNA abrogated the improvement in myocardial function induced by adiponectin. Infarct size following local ischaemia-reperfusion was 40 +/- 6% of the area at risk in the vehicle group. Adiponectin reduced infarct size to 19 +/- 2% (P < 0.01). L-NNA did not affect infarct size per se but abolished the protective effect of adiponectin (infarct size 40 +/- 5%). Phosphorylation of eNOS Ser1177, AMPK Thr172, and Akt Ser 473 was increased in the adiponectin group (P < 0.05).

CONCLUSION:

Adiponectin protects from myocardial contractile dysfunction and limits infarct size following ischaemia and reperfusion by a mechanism involving activation of AMPK and production of NO.

• Authors: Adrian T Gonon, Ulrika Widegren, Aliaksandr Bulhak, Firoozeh Salehzadeh, Jonas Persson, Per-Ove Sjöquist, John Pernow
• Journal: Cardiovascular research (Cardiovasc Res) Vol. 78 Issue 1 Pg. 116-22 (Apr 01 2008) ISSN: 0008-6363 [Print] England
• PMID: 18222959 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ADIPOQ protein, human
• Adiponectin
• Enzyme Inhibitors
• Multienzyme Complexes
• Nitroarginine
• Nitric Oxide
• Nitric Oxide Synthase Type II
• Nitric Oxide Synthase Type III
• Nos3 protein, rat
• Protein Serine-Threonine Kinases
• Proto-Oncogene Proteins c-akt
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases
• Adiponectin (metabolism)
• Animals
• Blotting, Western
• Coronary Circulation
• Disease Models, Animal
• Enzyme Inhibitors (pharmacology)
• Hemodynamics
• Humans
• Male
• Multienzyme Complexes (metabolism)
• Myocardial Contraction
• Myocardial Infarction (enzymology, pathology, prevention & control)
• Myocardial Reperfusion Injury (enzymology, physiopathology, prevention & control)
• Myocardium (enzymology, pathology)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type II (antagonists & inhibitors, metabolism)
• Nitric Oxide Synthase Type III
• Nitroarginine (pharmacology)
• Phosphorylation
• Protein Serine-Threonine Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Time Factors
• Ventricular Function, Left