Autophagy as a therapeutic target in cardiovascular disease

Andriy Nemchenko, Mario Chiong, Aslan Turer, Sergio Lavandero, Joseph A. Hill

Résultat de rechercheexamen par les pairs

150 Citations (Scopus)

Résumé

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."

Langue d'origineEnglish
Pages (de-à)584-593
Nombre de pages10
JournalJournal of Molecular and Cellular Cardiology
Volume51
Numéro de publication4
DOI
Statut de publicationPublished - oct. 2011

Financement

This work was supported by grants from the NIH ( HL-075173 , JAH; HL-080144 , JAH; HL-090842 , JAH), AHA ( 0640084N , JAH), ADA ( 7-08-MN-21-ADA , JAH), the AHA-Jon Holden DeHaan Foundation ( 0970518N , JAH), and the Fondo Nacional de Desarrollo Cientifico y Tecnologico, Chile ( FONDECYT 1080436 , SL; FONDAP 15010006 , SL). SL is on a sabbatical leave at the University of Texas Southwestern Medical Center, Dallas, Texas, USA.

Bailleurs de fondsNuméro du bailleur de fonds
AHA-Jon Holden DeHaan Foundation0970518N
National Institutes of HealthHL-080144, HL-090842
National Heart, Lung, and Blood InstituteR01HL075173
Fondo Nacional de Desarrollo Científico y Tecnológico
Aeronautical Development Agency
Fondo Nacional de Desarrollo Científico, Tecnológico y de Innovación Tecnológica1080436, FONDAP 15010006
Animal Health Australia0640084N

    ASJC Scopus Subject Areas

    • Molecular Biology
    • Cardiology and Cardiovascular Medicine

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