Autophagy as a therapeutic target in cardiovascular disease

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

Research output: Contribution to journalReview article

127 Scopus citations

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."

Original languageEnglish (US)
Pages (from-to)584-593
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Volume51
Issue number4
DOIs
StatePublished - Oct 1 2011

Keywords

  • AMPK
  • Autophagy
  • Cardiac hypertrophy
  • HDAC inhibitors
  • Heart failure
  • Hypertrophy
  • IP3
  • MTOR
  • P53
  • PKA
  • Plasticity
  • Remodeling

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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