We have previously shown that resveratrol possesses cardioprotective effect, 
which may be attributed to its ability to (i) stimulate nitric oxide production 
and (ii) free radical scavenging activity. Since resveratrol is one of the major 
components of certain varieties of red grapes, these events may underlie the 
cardioprotective effects thought to be obtained from moderate red wine 
consumption. Here we report resveratrol enhanced myocardial angiogenesis both in 
vivo and in vitro by induction of vascular endothelial growth factor (VEGF), 
which was regulated by thioredoxin-1 (Trx-1) and heme oxygenase-1 (HO-1). Human 
coronary arteriolar endothelial cells exposed to resveratrol or Trx-1 on 
Matrigel demonstrated significantly accelerated tubular morphogenesis with 
induction of HO-1 and VEGF expression. This angiogenic response was repressed by 
tin-protoporphyrin IX (SnPP), an HO-1 inhibitor, along with downregulation of 
VEGF expression. However Trx-1 expression was not affected by SnPP. Again, rat 
neonatal cardiomyocytes treated with resveratrol significantly expressed Trx-1, 
HO-1 as well as VEGF. Rats were orally administered with resveratrol (1 mg/kg 
per day) for 14 days and then underwent permanent left anterior descending 
coronary artery (LAD) occlusion to document similar pro-angiogenic effect. Our 
results demonstrated that pretreatment with resveratrol markedly reduced infarct 
size 24 h after myocardial infarction (MI) and increased capillary density in 
the peri-infarct myocardium along with better left ventricular function 4 days 
after MI compared with vehicle-treated control. Concomitantly, 
resveratrol-treated myocardium after MI significantly induced Trx-1, HO-1 and 
VEGF expression. This effect was blocked by SnPP. Our findings suggest that 
resveratrol mediates cardioprotection and neovascularization through 
Trx-1-HO-1-VEGF pathway in rat ischemic myocardium.