title: Myocardial stress and autophagy: mechanisms and potential therapies.
abstract: Autophagy is a ubiquitous cellular catabolic process responsive to energy stress. Research over the past decade has revealed that cardiomyocyte autophagy is a prominent homeostatic pathway, important in adaptation to altered myocardial metabolic demand. The cellular machinery of autophagy involves targeted direction of macromolecules and organelles for lysosomal degradation. Activation of autophagy has been identified as cardioprotective in some settings (that is, ischaemia and ischaemic preconditioning). In other situations, sustained autophagy has been linked with cardiopathology (for example, sustained pressure overload and heart failure). Perturbation of autophagy in diabetic cardiomyopathy has also been observed and is associated with both adaptive and maladaptive responses to stress. Emerging research findings indicate that various forms of selective autophagy operate in parallel to manage various types of catabolic cellular cargo including mitochondria, large proteins, glycogen, and stored lipids. In this Review, induction of autophagy associated with cardiac benefit or detriment is considered. The various static and dynamic approaches used to measure autophagy are critiqued, and current inconsistencies in the understanding of autophagy regulation in the heart are highlighted. The prospects for pharmacological intervention to achieve therapeutic manipulation of autophagic processes are also discussed.
authors.affiliation: School of Biomedical Sciences, University of Melbourne, Melbourne, Victoria 3010, Australia.
authors.forename: Lea M D
authors.initials: LMD
authors.lastname: Delbridge
authors.affiliation: Department of Physiology, Medical &Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland 1023, New Zealand.
authors.forename: Kimberley M
authors.initials: KM
authors.lastname: Mellor
authors.affiliation: Heart Institute, Cedars-Sinai Hospital, 127 South San Vicente Boulevard, Los Angeles, California 90048, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Taylor
authors.affiliation: Heart Institute, Cedars-Sinai Hospital, 127 South San Vicente Boulevard, Los Angeles, California 90048, USA.
authors.forename: Roberta A
authors.initials: RA
authors.lastname: Gottlieb
mesh_terms: D001343:Autophagy / Q000502:physiology*; D055808:Drug Discovery; D004734:Energy Metabolism; D006706:Homeostasis; D006801:Humans; D009206:Myocardium / Q000378:metabolism*; D013312:Stress, Physiological / Q000187:drug effects / Q000502:physiology