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 neointimal formation after balloon injury, suggesting the role of oxidative stress as a promotor of intimal cell proliferation. Heme oxygenase-1 (HO-1) is an inducible form of heme catabolizing enzyme that is induced by and acts against 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. Intraperitoneal administration of hemin, a HO-1 inducer, for 5 consecutive days resulted in about a 4-fold increase of serum bilirubin concentration. In addition, hemin injection increased HO-1 protein expression in the carotid artery, the heart, the kidney, and the liver. In this condition, balloon injury-induced neointimal formation was markedly inhibited. Local application of tin protoporphyrin, a HO inhibitor, blocked this effect, suggesting that induced HO-1 in the carotid artery was responsible for the inhibition of neointimal formation after balloon injury. This study suggests that induction of the endogenous antioxidant gene can suppress neointimal formation after balloon injury.
Aizawa
T
T
Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-8655, Japan. aizawa-tky@umin.ac.jp
Ishizaka
N
N
Taguchi
J
J
Kimura
S
S
Kurokawa
K
K
Ohno
M
M
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002339:Carotid Arteries / Q000201:enzymology* / Q000473:pathology; D020212:Carotid Artery Injuries; D002404:Catheterization / Q000009:adverse effects; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D015870:Gene Expression / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D051547:Heme Oxygenase-1; D006427:Hemin / Q000008:administration & dosage*; D008297:Male; D008665:Metalloporphyrins / Q000008:administration & dosage; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D011524:Protoporphyrins / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D004791:Enzyme Inhibitors; D008665:Metalloporphyrins; D011524:Protoporphyrins; D006427:Hemin; C032628:tin protoporphyrin IX; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1