Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart

Che Hong Chen, Grant R. Budas, Eric N. Churchill, Marie Hélène Disatnik, Thomas Hurley, Daria Mochly-Rosen

Research output: Contribution to journalArticle

451 Citations (Scopus)

Abstract

There is substantial interest in the development of drugs that limit the extent of ischemia-induced cardiac damage caused by myocardial infarction or by certain surgical procedures. Here, using an unbiased proteomic search, we identified mitochondrial aldehyde dehydrogenase 2 (ALDH2) as an enzyme whose activation correlates with reduced ischemic heart damage in rodent models. A high-throughput screen yielded a small-molecule activator of ALDH2 (Alda-1) that, when administered to rats before an ischemic event, reduced infarct size by 60%, most likely through its inhibitory effect on the formation of cytotoxic aldehydes. In vitro, Alda-1 was a particularly effective activator of ALDH2*2, an inactive mutant form of the enzyme that is found in 40% of East Asian populations. Thus, pharmacologic enhancement of ALDH2 activity may be useful for patients with wild-type or mutant ALDH2 who are subjected to cardiac ischemia, such as during coronary bypass surgery.

Original languageEnglish
Pages (from-to)1493-1495
Number of pages3
JournalScience
Volume321
Issue number5895
DOIs
StatePublished - Sep 12 2008

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Aldehyde Dehydrogenase
Ischemia
Enzyme Activation
Aldehydes
Proteomics
Rodentia
Myocardial Infarction
Enzymes
Pharmaceutical Preparations
Population

ASJC Scopus subject areas

  • General

Cite this

Chen, C. H., Budas, G. R., Churchill, E. N., Disatnik, M. H., Hurley, T., & Mochly-Rosen, D. (2008). Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart. Science, 321(5895), 1493-1495. https://doi.org/10.1126/science.1158554

Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart. / Chen, Che Hong; Budas, Grant R.; Churchill, Eric N.; Disatnik, Marie Hélène; Hurley, Thomas; Mochly-Rosen, Daria.

In: Science, Vol. 321, No. 5895, 12.09.2008, p. 1493-1495.

Research output: Contribution to journalArticle

Chen, CH, Budas, GR, Churchill, EN, Disatnik, MH, Hurley, T & Mochly-Rosen, D 2008, 'Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart', Science, vol. 321, no. 5895, pp. 1493-1495. https://doi.org/10.1126/science.1158554
Chen CH, Budas GR, Churchill EN, Disatnik MH, Hurley T, Mochly-Rosen D. Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart. Science. 2008 Sep 12;321(5895):1493-1495. https://doi.org/10.1126/science.1158554
Chen, Che Hong ; Budas, Grant R. ; Churchill, Eric N. ; Disatnik, Marie Hélène ; Hurley, Thomas ; Mochly-Rosen, Daria. / Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart. In: Science. 2008 ; Vol. 321, No. 5895. pp. 1493-1495.
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