The discovery of the protective effects of myocardial preconditioning has stimulated much research into the molecular mechanism of this phenomenon. A number of cardiac proteins have been found whose levels or state of phosphorylation change with cardioprotection, but do any of these play a critical role?
Chen et al. used unbiased proteomic analysis to identify an enzyme that consistently correlated with cardioprotection in a rat model, mitochondrial aldehyde dehydrogenase 2 (ALDH2). Further research identified a small molecule, Alda-1, which enhanced levels of ALDH2 and led to a 60% reduction in infarct size when it was injected into rats.
Several animal studies have found important cardioprotective proteins before and it remains to be seen whether ALDH2 and Alda-1 will be of any use in limitng myocardial ischaemia. On the other hand, the mechanisms described here provide attractive targets for future pharmaceutical agents on several fronts – ALDH2 is also important in the metabolism of alcohol.
- Chen C-H, Budas GR, Churchill EN et al. Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart. Science 2008; 321: 1493-1495.