Cardiovascular Research Advance Access originally published online on January 25, 2008
Cardiovascular Research 2008 78(1):116-122; doi:10.1093/cvr/cvn017
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Adiponectin protects against myocardial ischaemia-reperfusion injury via AMP-activated protein kinase, Akt, and nitric oxide
1 Department of Medicine, Unit of Cardiology, Karolinska Institutet, 171 77 Stockholm, Sweden
2 Department of Molecular Medicine and Surgery, Section of Integrative Physiology, Karolinska Institutet, 171 77 Stockholm, Sweden
3 Danderyd University Hospital, Karolinska Institutet, 171 77 Stockholm, Sweden
* Corresponding author: Department of Cardiology, Karolinska University Hospital, Solna, 171 76 Stockholm, Sweden. Tel: +46 8 517 70 000; fax: +46 8 31 10 40. E-mail address: adrgon{at}ki.se
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 µg/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.
KEYWORDS Adiponectin; Nitric oxide; Ischaemia; Reperfusion; Heart
Time for primary review: 29 days