The Importance of Autophagy in Cardioprotection

• Published in: High blood pressure & cardiovascular prevention Vol. 21; no. 1; pp. 21 - 28
• Main Authors: Sciarretta, Sebastiano, Yee, Derek, Shenoy, Varun, Nagarajan, Narayani, Sadoshima, Junichi
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.03.2014; Springer Nature B.V
• Subjects: Adenosine triphosphate; Aging; Amino acids; Apoptosis; Autophagy; Autophagy - physiology; Cardiology; Cardiomyocytes; Cardiomyopathy; Energy; Enzymes; Fatty acids; Heart failure; Heart Failure - physiopathology; Heart Failure - prevention & control; Humans; Ischemia; Kinases; Lysosomes - physiology; Mechanistic Target of Rapamycin Complex 1; Medicine; Medicine & Public Health; Metabolic syndrome; Mitochondria; Monomeric GTP-Binding Proteins - physiology; Multiprotein Complexes - physiology; Myocardial Infarction - physiopathology; Myocardial Infarction - prevention & control; Myocardial Ischemia - physiopathology; Myocardial Ischemia - prevention & control; Neuropeptides - physiology; Pharmacotherapy; Phosphorylation; Physiology; Proteins; Ras Homolog Enriched in Brain Protein; Review Article; Signal Transduction - physiology; TOR Serine-Threonine Kinases - physiology; mTOR; Obesity; Cardioprotection; Ischemia; Autophagy
• ISSN: 1120-9879; 1179-1985
• DOI: 10.1007/s40292-013-0029-9

Autophagy is an intracellular lysosomal-mediated catabolic process in which senescent or damaged proteins and organelles are sequestered by double membrane-limited vesicles called autophagosomes, and then degraded by lysosomes. While the role of autophagy in different pathological states is context-dependent, it has been shown that during cardiac ischemia, autophagy is upregulated as a cardioprotective adaptation. We recently demonstrated that Rheb, a small GTP-binding protein that directly activates the complex 1 of the mechanistic target of rapamycin, is a critical regulator of autophagy during cardiac ischemia. We found that cardiac Rheb/mTORC1 signaling is activated in a deregulated manner during ischemia in obesity and metabolic syndrome. This uncontrolled activation of the Rheb/mTORC1 pathway leads to autophagy inhibition and to a reduction of myocardial tolerance to ischemia. This data further supports the relevance of autophagy as a fundamental protective mechanism during myocardial ischemia and suggests that reactivation of autophagy, in particular through the inhibition of Rheb/mTORC1 signaling may represent a promising therapeutic option to treat subjects with an acute myocardial infarction, particularly those affected by metabolic derangements. This review will deal with the biological significance of autophagy in cardioprotection.