Aldehyde dehydrogenase 2 in cardiac protection: a new therapeutic target?

Trends Cardiovasc Med. 2009 Jul;19(5):158-64. doi: 10.1016/j.tcm.2009.09.003.

Abstract

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is emerging as a key enzyme involved in cytoprotection in the heart. ALDH2 mediates both the detoxification of reactive aldehydes such as acetaldehyde and 4-hydroxy-2-nonenal and the bioactivation of nitroglycerin to nitric oxide. In addition, chronic nitrate treatment results in ALDH2 inhibition and contributes to nitrate tolerance. Our laboratory recently identified ALDH2 to be a key mediator of endogenous cytoprotection. We reported that ALDH2 is phosphorylated and activated by the survival kinase protein kinase C epsilon and found a strong inverse correlation between ALDH2 activity and infarct size. We also identified a small molecule ALDH2 activator which reduces myocardial infarct size induced by ischemia/reperfusion in vivo. In this review, we discuss evidence that ALDH2 is a key mediator of endogenous survival signaling in the heart, suggest possible cardioprotective mechanisms mediated by ALDH2 and discuss potential clinical implications of these findings.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aldehyde Dehydrogenase / genetics
  • Aldehyde Dehydrogenase / metabolism*
  • Aldehyde Dehydrogenase, Mitochondrial
  • Animals
  • Cytoprotection*
  • Humans
  • Ischemic Preconditioning, Myocardial
  • Myocardial Infarction / enzymology*
  • Myocardial Reperfusion Injury / enzymology
  • Myocardium / enzymology*
  • Phosphorylation
  • Protein Kinase C / metabolism
  • Signal Transduction

Substances

  • ALDH2 protein, human
  • Aldehyde Dehydrogenase
  • Aldehyde Dehydrogenase, Mitochondrial
  • Protein Kinase C