title: Autophagy as a therapeutic target in cardiovascular disease.
abstract: The epidemic of heart failure continues apace, and development of novel therapies with clinical efficacy has lagged. Now, important insights into the molecular circuitry of cardiovascular autophagy have raised the prospect that this cellular pathway of protein quality control may be a target of clinical relevance. Whereas basal levels of autophagy are required for cell survival, excessive levels - or perhaps distinct forms of autophagic flux - contribute to disease pathogenesis. Our challenge will be to distinguish mechanisms that drive adaptive versus maladaptive autophagy and to manipulate those pathways for therapeutic gain. Recent evidence suggests this may be possible. Here, we review the fundamental biology of autophagy and its role in a variety of forms of cardiovascular disease. We discuss ways in which this evolutionarily conserved catabolic mechanism can be manipulated, discuss studies presently underway in heart disease, and provide our perspective on where this exciting field may lead in the future. This article is part of a special issue entitled ''Key Signaling Molecules in Hypertrophy and Heart Failure.''
authors: Department of Internal Medicine (Cardiology), University of Texas Southwestern Medical Center, Dallas, Texas 75235, USA.
authors: Andriy
authors: A
authors: Nemchenko
authors: Mario
authors: M
authors: Chiong
authors: Aslan
authors: A
authors: Turer
authors: Sergio
authors: S
authors: Lavandero
authors: Joseph A
authors: JA
authors: Hill
mesh_terms: D000263:Adenylate Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D006332:Cardiomegaly / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002317:Cardiovascular Agents / Q000627:therapeutic use; D042002:Chromatin Assembly and Disassembly; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051548:Histone Acetyltransferases / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D000076222:Mechanistic Target of Rapamycin Complex 1; D058990:Molecular Targeted Therapy; D046912:Multiprotein Complexes; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011506:Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases; D016159:Tumor Suppressor Protein p53 / Q000819:agonists / Q000378:metabolism
chemical_list: D002317:Cardiovascular Agents; D056572:Histone Deacetylase Inhibitors; D053496:Inositol 1,4,5-Trisphosphate Receptors; D046912:Multiprotein Complexes; D011506:Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051548:Histone Acetyltransferases; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D000263:Adenylate Kinase; D006655:Histone Deacetylases