title: Autophagy: a target for therapeutic interventions in myocardial pathophysiology.
abstract: BACKGROUND
  Autophagy is a major degradative and highly conserved process in eukaryotic cells that is activated by stress signals. This self-cannibalisation is activated as a response to changing environmental conditions, cellular remodelling during development and differentiation, and maintenance of homeostasis.
  
  
  OBJECTIVE
  To review autophagy regarding its process, molecular mechanisms and regulation in mammalian cells, and its role in myocardial pathophysiology.
  
  
  CONCLUSIONS
  Autophagy is a multistep process regulated by diverse, intracellular and/or extracellular signalling complexes and pathways. In the heart, normally, autophagy occurs at low basal levels, where it represents a homeostatic mechanism for the maintenance of cardiac function and morphology. However, in the diseased heart the functional role of the enhanced autophagy is unclear and studies have yielded conflicting results. Recently, it was shown that during myocardial ischemia autophagy promotes survival by maintaining energy homeostasis. Also, rapamycin was demonstrated to prevent cardiac hypertrophy. In heart failure, upregulation of autophagy acts as an adaptive response that protects cells from hemodynamic stress. In addition, sirolimus-eluting stents have been shown to lower re-stenosis rates in patients with coronary artery disease after angioplasty. Thus, this mechanism can become a major target for therapeutic intervention in heart pathophysiology.
authors.affiliation: National and Kapodistrian University of Athens, Medical School, Department of Experimental Physiology, Goudi-Athens, Greece.
authors.forename: Antonis
authors.initials: A
authors.lastname: Halapas
authors.forename: Athanasios
authors.initials: A
authors.lastname: Armakolas
authors.forename: Michael
authors.initials: M
authors.lastname: Koutsilieris
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D051379:Mice; D051381:Rats; D015398:Signal Transduction