Induction of autophagy contributes to the myocardial protection of valsartan against ischemia‑reperfusion injury.

Abstract

The mechanisms underlying the myocardial protection of valsartan against ischemia/reperfusion (I/R) injury are complicated and remain unclear. The aim of this study was to investigate whether autophagy machinery was involved in the protection against I/R injury that is induced by valsartan. In vivo rat hearts were subjected to ischemia by 30 min ligation of the left anterior descending coronary artery, followed by a 120 min reperfusion. 3‑methyladenine (3‑MA), a specific inhibitor on autophagic sequestration, was used to inhibit autophagy. The hemodynamics, infarct size of the ventricle and LC3B protein were measured. Western blot analysis was performed to investigate the mechanism by which autophagy was induced by valsartan. Valsartan preconditioning resulted in a significant decrease in infarct size and induced autophagy in the rat heart subjected to I/R injury. The hemodynamics assay showed that the valsartan‑induced cardiac functional recovery was attenuated by 3‑MA. By contrast, 3‑MA decreased the improvement induced by valsartan on the histology and infarction of the rat heart subjected to I/R injury. Valsartan preconditioning induced autophagy via the AKT/mTOR/S6K pathway, independent of Beclin1. In conclusion, valsartan preconditioning induced autophagy via the AKT/mTOR/S6K pathway, which contributed to the myocardial protection against I/R injury.

• Authors: Xiaoqian Wu, Lishan He, Yi Cai, Guiping Zhang, Yulian He, Zhijia Zhang, Xiaoen He, Yanhua He, Genshui Zhang, Jiandong Luo
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 8 Issue 6 Pg. 1824-30 (Dec 2013) ISSN: 1791-3004 [Electronic] Greece
• PMID: 24084854 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cardiotonic Agents
• Tetrazoles
• 3-methyladenine
• Valsartan
• Proto-Oncogene Proteins c-akt
• Ribosomal Protein S6 Kinases
• TOR Serine-Threonine Kinases
• Valine
• Adenine

Topics

• Adenine (analogs & derivatives, pharmacology)
• Animals
• Autophagy (drug effects)
• Cardiotonic Agents (pharmacology, therapeutic use)
• Hemodynamics (drug effects)
• Ischemic Preconditioning
• Male
• Myocardial Infarction (drug therapy, pathology, physiopathology)
• Myocardial Reperfusion Injury (drug therapy, pathology, physiopathology, prevention & control)
• Myocardium (pathology, ultrastructure)
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats
• Rats, Sprague-Dawley
• Ribosomal Protein S6 Kinases (metabolism)
• Signal Transduction (drug effects)
• TOR Serine-Threonine Kinases (metabolism)
• Tetrazoles (pharmacology, therapeutic use)
• Valine (analogs & derivatives, pharmacology, therapeutic use)
• Valsartan