Induction of heme oxygenase-1 can act protectively against cardiac ischemia/reperfusion in vivo.
Enhanced production of reactive oxygen species plays a role in myocardial injury following ischemia/reperfusion. Heme oxygenase-1 (HO-1) is a heme-catabolizing enzyme that is induced by and acts against oxidant-induced tissue injury. We examined whether HO-1 expression was regulated following ischemia and reperfusion in the rat heart. HO-1 expression increased as early as 24 h after reperfusion. Strong HO-1 expression was seen in monocytes/macrophages and myofibroblasts. Next, we examined whether the induction of HO-1 could ameliorate cardiac injury following ischemia/reperfusion. Intraperitoneal hemin injection (30 mg/kg/day) for 2 days prior to the operation resulted in an about 2.8-fold increase in HO-1 expression in the rat heart. Hemin treatment significantly decreased infarct area (6 +/- 2%) compared to the control (21 +/- 2%), which was reversed by the coadministration of an HO inhibitor in a dose-dependent manner. Our data suggest that induction of HO-1 can reduce the cardiac injury in vivo following ischemia/reperfusion.
Hangaishi
M
M
Department of Cardiovascular Medicine, University of Tokyo, Graduate School of Medicine, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-8655, Japan.
Ishizaka
N
N
Aizawa
T
T
Kurihara
Y
Y
Taguchi
J
J
Nagai
R
R
Kimura
S
S
Ohno
M
M
D000818:Animals; D003971:Diastole; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006339:Heart Rate; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis / Q000235:genetics*; D051547:Heme Oxygenase-1; D006427:Hemin / Q000494:pharmacology; D006439:Hemodynamics / Q000502:physiology*; D007700:Kinetics; D017202:Myocardial Ischemia / Q000201:enzymology / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013599:Systole; D013997:Time Factors
D006427:Hemin; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1