Autophagy modulation: a potential therapeutic approach in cardiac hypertrophy

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 313; no. 2; pp. H304 - H319
• Main Authors: Wang, Xuejun, Cui, Taixing
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.08.2017
• Series: Heart Failure: Novel Therapeutic Pathways Emerging from Basic Science
• Subjects: Animals; Autophagy; Blood pressure; Cardiomegaly - metabolism; Cardiomegaly - pathology; Cardiomegaly - physiopathology; Cardiomegaly - therapy; Cardiovascular system; Catabolism; Cytoplasm; Heart failure; Heart Failure - metabolism; Heart Failure - pathology; Heart Failure - physiopathology; Heart Failure - therapy; Humans; Lysosomes - metabolism; Lysosomes - pathology; Myocardium - metabolism; Myocardium - pathology; Quality control; Review; Signal Transduction; transcription factor EB; autophagy; mechanistic target of rapamycin; cardiac hypertrophy; pressure overload
• ISSN: 0363-6135; 1522-1539; 1522-1539
• DOI: 10.1152/ajpheart.00145.2017

Autophagy is an evolutionarily conserved process used by the cell to degrade cytoplasmic contents for quality control, survival for temporal energy crisis, and catabolism and recycling. Rapidly increasing evidence has revealed an important pathogenic role of altered activity of the autophagosome-lysosome pathway (ALP) in cardiac hypertrophy and heart failure. Although an early study suggested that cardiac autophagy is increased and that this increase is maladaptive to the heart subject to pressure overload, more recent reports have overwhelmingly supported that myocardial ALP insufficiency results from chronic pressure overload and contributes to maladaptive cardiac remodeling and heart failure. This review examines multiple lines of preclinical evidence derived from recent studies regarding the role of autophagic dysfunction in pressure-overloaded hearts, attempts to reconcile the discrepancies, and proposes that resuming or improving ALP flux through coordinated enhancement of both the formation and the removal of autophagosomes would benefit the treatment of cardiac hypertrophy and heart failure resulting from chronic pressure overload.