Balloon injury does not induce heme oxygenase-1 expression, but administration of hemin inhibits neointimal formation in balloon-injured rat carotid artery

It has been shown that antioxidant agents act inhibitorily against neointim al formation after balloon injury, suggesting the role of oxidative stress as a promotor of intimal cell proliferation. Heme oxygenase-l (HO-1) is an inducible form of heme catabolizing enzyme that is induced by and acts agai nst oxidative tissue injury. In this set of experiments, we showed that HO- 1 was present in newly formed neointima; however, arterial HO-1 expression did not increase in response to balloon injury in rat carotid artery. Intra peritoneal administration of hemin, a HO-1 inducer, for 5 consecutive days resulted in about a 4-fold increase of serum bilirubin concentration. In ad dition, hemin injection increased HO-1 protein expression in the carotid ar tery, the heart, the kidney, and the liver. In this condition, balloon inju ry-induced neointimal formation was markedly inhibited. Local application o f tin protoporphyrin, a HO inhibitor, blocked this effect, suggesting that induced HO-1 in the carotid artery was responsible for the inhibition of ne ointimal formation after balloon injury. This study suggests that induction of the endogenous antioxidant gene can suppress neointimal formation after balloon injury. (C) 1999 Academic Press.