Protective role of heme oxygenase in the blood vessel wall during atherogenesis.
Several lines of evidence suggest that antioxidant processes and (or) endogenous antioxidants inhibit proatherogenic events in the blood vessel wall. Heme oxygenase (HO), which catabolizes heme to biliverdin, carbon monoxide, and catalytic iron, has been shown to have such antioxidative properties. The HO-1 isoform of heme oxygenase is ubiquitous and can be increased several fold by stimuli that induce cellular oxidative stress. Products of the HO reaction have important effects: carbon monoxide is a potent vasodilator, which is thought to play a role in modulation of vascular tone; biliverdin and its by-product bilirubin are potent antioxidants. Although HO induction results in an increase in catalytic free iron release, the enhancement of intracellular ferritin protein through HO-1 has been reported to decrease the cytotoxic effects of iron. Oxidized LDL has been shown to increase HO-1 expression in endothelial and smooth muscle cell cultures, and during atherogenesis. Further evidence of HO-1 expression associated with atherogenesis has been demonstrated in human, murine and rabbit atherosclerotic lesions. Moreover, genetic models of HO deficiency suggest that the actions of HO-1 are important in modulating the severity of atherosclerosis. Recent experiments in gene therapy using the HO gene suggest that interventions aimed at HO in the vessel wall could provide a novel therapeutic approach for the treatment or prevention of atherosclerotic disease.
Hoekstra
Kenneth A
KA
Faculty of Agricultural Sciences, 2357 Main Mall, Vancouver, BC V6T 1Z4, Canada. khoekstra@langara.bc.ca
Godin
David V
DV
Cheng
Kimberly M
KM
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001161:Arteriosclerosis / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D001663:Bilirubin / Q000378:metabolism; D001664:Biliverdine / Q000378:metabolism; D001808:Blood Vessels / Q000201:enzymology* / Q000473:pathology; D002248:Carbon Monoxide / Q000378:metabolism; D004730:Endothelium, Vascular / Q000201:enzymology* / Q000473:pathology; D005293:Ferritins / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D015316:Genetic Therapy; D006418:Heme / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D018384:Oxidative Stress
D000975:Antioxidants; D007527:Isoenzymes; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D006418:Heme; D002248:Carbon Monoxide; D005293:Ferritins; D006419:Heme Oxygenase (Decyclizing); D001664:Biliverdine; D001663:Bilirubin