AMP-activated protein kinase deficiency enhances myocardial ischemia/reperfusion injury but has minimal effect on the antioxidant/antinitrative protection of adiponectin.

Authors

• Yajing Wang
• Erhe Gao
• Ling Tao
• Wayne Bond Lau
• Yuexin Yuan
• Barry J Goldstein
• Bernard L Lopez
• Theodore A Christopher
• Rong Tian
• Walter Koch
• Xin-Liang Ma

Publication/Presentation Date

2-17-2009

Abstract

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 AMPKalpha2 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.

Volume

119

Issue

6

First Page

835

Last Page

844

ISSN

1524-4539

Published In/Presented At

Wang, Y., Gao, E., Tao, L., Lau, W. B., Yuan, Y., Goldstein, B. J., Lopez, B. L., Christopher, T. A., Tian, R., Koch, W., & Ma, X. L. (2009). AMP-activated protein kinase deficiency enhances myocardial ischemia/reperfusion injury but has minimal effect on the antioxidant/antinitrative protection of adiponectin. Circulation, 119(6), 835–844. https://doi.org/10.1161/CIRCULATIONAHA.108.815043

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

19188503

Department(s)

Administration and Leadership

Document Type

Article