Angiotensin II (AngII) type 1 receptor (AT1R) blockers (ARBs) limit left ventricular (
LV) dysfunction and
necrosis after reperfused
myocardial infarction (RMI) and proteomics can detect changes in
protein levels after injury. We applied proteomics to detect changes in levels of specific
protein in the ischemic zone (IZ) and non-ischemic zone (NIZ) of dog hearts after in vivo RMI (90 min of anterior
ischemia; 120 min of reperfusion) and treatment with intravenous vehicle (control) and the ARBs
valsartan or
irbesartan (10 mg/kg) over 30 min before RMI. We also assessed LV function,
infarction and apoptosis. Both ARBs limited the RMI-induced
LV dysfunction,
infarct size and apoptosis. Proteomics detected differential expression of 5 randomly selected
proteins in the IZ compared to the NIZ after RMI: decrease in α subunit of
ATP synthase
isoform precursor (consistent with increased conversion to α subunit under metabolic stress), M chain
creatine kinase (consistent with cellular damage) and
ventricular myosin light chain-1 (consistent with structural damage and decreased contractility); and increase in
NAD(+)-isocitrate dehydrogenase (ICDH) and α subunit and
ATP synthase D chain (mitochondrial, consistent with metabolic dysfunction). Importantly, changes in
NAD+-ICDH and
ATP synthase D chain were reversed by ARB
therapy. Thus, proteomics can detect regional changes in metabolic, contractile, and structural
proteins after RMI and several of these
proteins are favorably modified by ARBs, suggesting that they may be novel therapeutic targets. (Mol Cell Biochem 263: 179-188, 2004).