“…Our group (1,36) reported previously that predelivery of antioxidant genes such as heme oxygenase-1 (HO-1) or extracellular superoxide dismutase to the myocardium provides a preemptive strategy for myocardial protection in the event of MI. HO-1, in particular, may be well suited as a therapeutic agent for myocardial protection, because the catabolic byproducts of heme metabolism, carbon monoxide (CO) and bilirubin, have been reported to exert pleiotropic cytoprotective effects, including reduction of oxidative stress (4,44,52), inflammation (39,57), and apoptosis (2,14,28,36,40,54), which are the principal pathological stimuli leading to irreversible myocardial damage following ischemia and reperfusion (I/R) (7,13,54).…”