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Cardiovascular disease

Enhanced protection of the heart

Nature Reviews Drug Discovery volume 7, page 892 (2008)Cite this article

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Initial proteomic studies identified mitochondrial ALDH2 as the only protein for which phosphorylation status consistently correlated with cardioprotection in homogenates of ischaemic rat hearts preconditioned by treatment with ethanol or an activator of protein kinase Cε (PKCε). Further studies in intact rat hearts showed that ALDH2 activity — stimulated by alcohol or a PKCε agonist, or inhibited by a PKCε antagonist, cyanamide or nitroglycerin — correlated with a reduction in infarct size following ischaemia.

This correlation does not necessarily mean that ALDH2 activation is sufficient to induce cardioprotection. So, to clarify this issue, the authors used high-throughput screening to search for agonists of ALDH2 and identified N-(1,3-benzodioxal-5-methyl)-2,6-dichlorobenzamide (Alda-1) as one of the more potent agonists.

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ORIGINAL RESEARCH PAPER

  1. Chen, C.-H. et al. Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart. Science 321, 1493–1495 (2008)

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  1. Man Tsuey Tse
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Tse, M. Enhanced protection of the heart. Nat Rev Drug Discov 7, 892 (2008). https://doi.org/10.1038/nrd2736

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