Mechanical Stretch-Induced Protection against Myocardial Ischemia- Reperfusion Injury Involves AMP-Activated Protein Kinase

• Published in: The Korean journal of physiology & pharmacology Vol. 14; no. 1; pp. 1 - 9
• Main Authors: Hao, Jia, Kim, Hun-Sik, Choi, Woong, Ha, Tae Sun, Ahn, Hee-Yul, Kim, Chan-Hyung
• Format: Journal Article
• Language: English
• Published: Korea (South) 대한생리학회-대한약리학회 01.02.2010; The Korean Journal of Physiology & Pharmacology Editorial Office; The Korean Physiological Society and The Korean Society of Pharmacology; 대한약리학회
• Subjects: Original; 약리학; Ischemia-reperfusion; Stretch; Cardioprotection; AMP-activated protein kinase
• ISSN: 1226-4512; 2093-3827
• DOI: 10.4196/kjpp.2010.14.1.1

AMP-activated protein kinase (AMPK) protects various tissues and cells from ischemic insults and is activated by many stimuli including mechanical stretch. Therefore, this study investigated if the activation of AMPK is involved in stretch-induced cardioprotection (SIC). Intraventricular balloon and aorto-caval shunt (ACS) were used to stretch rat hearts ex vivo and in vivo, respectively. Stretch preconditioning reduced myocardial infarct induced by ischemia-reperfusion (I/R) and improved post-ischemic functional recovery. Phosphorylation of AMPK and its downstream substrate, acetyl-CoA carboxylase (ACC) were increased by mechanical stretch and ACC phosphorylation was completely blocked by the AMPK inhibitor, Compound C. AMPK activator (AICAR) mimicked SIC. Gadolinium, a blocker of stretch-activated ion channels (SACs), inhibited the stretch-induced phosphorylation of AMPK and ACC, whereas diltiazem, a specific L-type calcium channel blocker, did not affect AMPK activation. Furthermore, SIC was abrogated by Compound C and gadolinium. The in vivo stretch induced by ACS increased AMPK activation and reduced myocardial infarct. These findings indicate that stretch preconditioning can induce the cardioprotection against I/R injury, and activation of AMPK plays an important role in SIC, which might be mediated by SACs.