title: The role and modulation of autophagy in experimental models of myocardial ischemia-reperfusion injury.
abstract: A physiological sequence called autophagy qualitatively determines cellular viability by removing protein aggregates and damaged cytoplasmic constituents, and contributes significantly to the degree of myocardial ischemia-reperfusion (I/R) injury. This tightly orchestrated catabolic cellular 'housekeeping' process provides cells with a new source of energy to adapt to stressful conditions. This process was first described as a pro-survival mechanism, but increasing evidence suggests that it can also lead to the demise of the cell. Autophagy has been implicated in the pathogenesis of multiple cardiac conditions including myocardial I/R injury. However, a debate persists as to whether autophagy acts as a protective mechanism or contributes to the injurious effects of I/R injury in the heart. This controversy may stem from several factors including the variability in the experimental models and species, and the methodology used to assess autophagy. This review provides updated knowledge on the modulation and role of autophagy in isolated cardiac cells subjected to I/R, and the growing interest towards manipulating autophagy to increase the survival of cardiac myocytes under conditions of stress-most notably being I/R injury. Perturbation of this evolutionarily conserved intracellular cleansing autophagy mechanism, by targeted modulation through, among others, mammalian target of rapamycin (mTOR) inhibitors, adenosine monophosphate-activated protein kinase (AMPK) modulators, calcium lowering agents, resveratrol, longevinex, sirtuin activators, the proapoptotic gene Bnip3, IP3 and lysosome inhibitors, may confer resistance to heart cells against I/R induced cell death. Thus, therapeutic manipulation of autophagy in the challenged myocardium may benefit post-infarction cardiac healing and remodeling.
authors.affiliation: VA Ann Arbor Health Care System, University of Michigan, 2215 Fuller Rd, Ann Arbor, MI 48105, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Chen-Scarabelli
authors.affiliation: Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai Medical Center, One Gustave L. Levy Place, Box 1030, New York, NY 10029-6574, USA.
authors.forename: Pratik R
authors.initials: PR
authors.lastname: Agrawal
authors.affiliation: St John Hospital and Medical Center, Wayne State University School of Medicine, 22101 Moross Rd., Detroit, MI 48236, USA.
authors.forename: Louis
authors.initials: L
authors.lastname: Saravolatz
authors.affiliation: St John Hospital and Medical Center, Wayne State University School of Medicine, 22101 Moross Rd., Detroit, MI 48236, USA.
authors.forename: Cadigia
authors.initials: C
authors.lastname: Abuniat
authors.affiliation: St John Hospital and Medical Center, Wayne State University School of Medicine, 22101 Moross Rd., Detroit, MI 48236, USA.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Scarabelli
authors.affiliation: Medical and Molecular Biology Unit, University College London, UCL, 30 Guildford St., London, WC1N 1EH, UK.
authors.forename: Anastasis
authors.initials: A
authors.lastname: Stephanou
authors.affiliation: St John Hospital and Medical Center, Wayne State University School of Medicine, 22101 Moross Rd., Detroit, MI 48236, USA.
authors.forename: Leena
authors.initials: L
authors.lastname: Loomba
authors.affiliation: Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai Medical Center, One Gustave L. Levy Place, Box 1030, New York, NY 10029-6574, USA.
authors.forename: Jagat
authors.initials: J
authors.lastname: Narula
authors.affiliation: Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai Medical Center, One Gustave L. Levy Place, Box 1030, New York, NY 10029-6574, USA ; St John Hospital and Medical Center, Wayne State University School of Medicine, 22101 Moross Rd., Detroit, MI 48236, USA.
authors.forename: Tiziano M
authors.initials: TM
authors.lastname: Scarabelli
authors.affiliation: Medical and Molecular Biology Unit, University College London, UCL, 30 Guildford St., London, WC1N 1EH, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Knight
keywords: Autophagy; Cell survival; Heart; Ischemia-reperfusion injury