The cardioprotective effect of heme oxygenase-1overexpression
T.V. Kukoba, Kotsuruba, A.A. Moibenko
О.О. Bogomolets Institute of Physiology, National Academyof Sciences of Ukraine, Kyiv
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Abstract
The purpose of this study was to determine the protective
effects of heme oxygenase-1 (HO-1) expression against pos-
tischemic myocardial dysfunction. We also investigated HO-1
expression in cardiac tissue from the left and right ventricles of
myocardium. Rat hearts were isolated and perfused according
to Langendorff technique to evaluate the recovery of myocar-
dial function after 20 min of global ischemia and 40 min of
reperfusion. We found that HO-1 expression was more ex-
pressed in left ventricles of myocardium in basic conditions
and after ischemia/reperfusion as well as after its previous
induction by hemin. Upregulation of the inducible isoform of
HO-1 and increase its activity after treatment of animals with
hemin 24 h before ischemia ameliorated myocardial function
(raised left ventricular developed pressure, decreased end-di-
astolic pressure, attenuated vasoconstriction) and reduced
oxydative stress in cardiac tissue during reperfusion of iso-
lated hearts. Zinc protoporphyrin IX, an inhibitor of heme
oxygenase activity, completely abolished the HO-1 expres-
sion in left ventricles of myocardium and increased postis-
chemic myocardial dysfunction. Likewise, cardiac tissue in-
jury was exacerbated by treatment with zinc protoporphyrin
IX through significant inhibition of HO activity and increasing
of hydroxyl radical production on reperfusion. The treatment
of animals with hemin and following ischemia/reperfusion re-
sulted in 5-6-times increase of HO-1 expression in the left
ventricle of myocardium whereas in right ventricle only in 3-
times. Our data provide strong evidence for a primary role of
HO-1 in cardioprotection against reperfusion injury and show
different HO-1 expression in left and right ventricles of myo-
cardium.
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