Heme oxygenase as an intrinsic defense system in vascular wall: implication against atherogenesis.
Recent developments in our understanding of the atherosclerotic process and factors that trigger ischemic cardiovascular disease have led to the consideration of antioxidative responses or exogenous antioxidants, which are proposed to inhibit multiple proatherogenic and prothrombotic events in arterial wall. Heme oxygenases (HO), an enzyme essential for heme degradation, have been shown to have such antioxidative properties via the production of bile pigments, carbon monoxide and ferritin induction. We have demonstrated that mildly oxidized LDL markedly induces HO-1, an inducible form of HO, in human aortic endothelial and smooth muscle cell cocultures and that its induction results in the attenuation of monocyte chemotaxis induced by mildly oxidized LDL. We also confirmed abundant expression of HO-1 in human, murine and rabbit atherosclerotic lesions. By modulating HO activities in LDL-receptor knockout mice and Watanabe heritable hyperlipidemic rabbits during their atherosclerotic lesion developments, anti-atherogenic properties of HO have demonstrated as judged by the quantitative analyses of atherosclerotic lesion formation. HO expression was inversely correlated with the levels of plasma and tissue lipid peroxides. HO also influenced on nitric oxide pathway. These observations may suggest that HO, induced during atherosclerotic process, functions as an intrinsic protective pathway in vascular wall.
Ishikawa
K
K
The First Department of Internal Medicine, Fukushima Medical University, Japan. kishikaw@fmu.ac.jp
Maruyama
Y
Y
D000818:Animals; D001161:Arteriosclerosis / Q000503:physiopathology* / Q000517:prevention & control; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress; D011817:Rabbits; D017539:Tunica Intima / Q000502:physiology*
D006419:Heme Oxygenase (Decyclizing)