AMP-Activated Protein Kinase Deficiency Enhances Myocardial Ischemia/Reperfusion Injury but Has Minimal Effect on the Antioxidant/Antinitrative Protection of Adiponectin

Article

关键词: VASCULAR ENDOTHELIAL-CELLS;    ISCHEMIA-REPERFUSION INJURY;    FATTY-ACID OXIDATION;    GLUCOSE-UPTAKE;    NITRIC-OXIDE;    STIMULATES ANGIOGENESIS;    SKELETAL-MUSCLE;    GLOBULAR DOMAIN;    SHORT-TERM;    CARDIOPROTECTION;   

DOI  :  10.1161/CIRCULATIONAHA.108.815043

来源: SCIE

【 摘 要 】

Background-Diabetes increases the morbidity/mortality of ischemic heart disease, but the underlying mechanisms are incompletely understood. Deficiency of both AMP-activated protein kinase (AMPK) and adiponectin occurs in diabetes, but whether AMPK is cardioprotective or a central mediator of adiponectin cardioprotection in vivo remains unknown. Methods and Results-Male adult mice with cardiomyocyte-specific overexpression of a mutant AMPK alpha(2) subunit (AMPK-DN) or wild-type (WT) littermates were subjected to in vivo myocardial ischemia/reperfusion (MI/R) and treated with vehicle or adiponectin. In comparison to WT, AMPK-DN mice subjected to MI/R endured greater cardiac injury (larger infarct size, more apoptosis, and poorer cardiac function) likely as a result of increased oxidative stress in these animals. Treatment of AMPK-DN mice with adiponectin failed to phosphorylate cardiac acetyl-CoA carboxylase as it did in WT mouse heart. However, a significant portion of the cardioprotection of adiponectin against MI/R injury was retained in AMPK-DN mice. Furthermore, treatment of AMPK-DN mice with adiponectin reduced MI/R-induced cardiac oxidative and nitrative stress to the same degree as that seen in WT mice. Finally, treating AMPK-DN cardiomyocytes with adiponectin reduced simulated MI/R-induced oxidative/nitrative stress and decreased cell death (P<0.01). Conclusions-Collectively, our results demonstrated that AMPK deficiency significantly increases MI/R injury in vivo but has minimal effect on the antioxidative/antinitrative protection of adiponectin. (Circulation. 2009;119:835-844.)

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