An Activator of Mutant and Wildtype Aldehyde Dehydrogenase Reduces Ischemic Damage to the Heart
By Che-Hong Chen, G. Budas, E. Churchill, M. Disatnik, Thomas D. Hurley, D. Mochly‐Rosen. Science, 2008
748 citations recorded by the source corpus.
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.
Subfields: Cardiology and Cardiovascular Medicine, Emergency Medicine, Pathology and Forensic Medicine
View Paper: https://www.semanticscholar.org/paper/833e53bdf38599d584157df1bae79b362fa1b089
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In Pathology and Forensic Medicine
Citations in the corpus
- The protective role of estrogen and estrogen receptors in cardiovascular disease and the controversial use of estrogen therapy (2017, background): “Activation of ALDH has previously been reported to protect the heart against ischemic damage [21].”
- Ischemia and reperfusion—from mechanism to translation (2011, background): “Other studies of metabolic adaptation during ischemia and reperfusion have shown that activation of mitochondrial aldehyde dehydrogenase 2 (ALDH2) is associated with robust cardioprotection in rat model”