Related Experiment Videos
Heme oxygenase as an intrinsic defense system in vascular wall: implication against atherogenesis
1The First Department of Internal Medicine, Fukushima Medical University, Japan. kishikaw@fmu.ac.jp
Insights
Heme oxygenases (HO) exhibit antioxidative properties, protecting against atherosclerosis. This study demonstrates HO-1 induction in atherosclerotic lesions, highlighting its intrinsic protective role in the vascular wall.
Area of Science:
- Cardiovascular Biology
- Enzymology
- Oxidative Stress Research
Background:
- Atherosclerosis involves proatherogenic and prothrombotic events in the arterial wall.
- Antioxidative responses, including exogenous antioxidants, are being explored to mitigate these events.
- Heme oxygenases (HO) possess antioxidative properties through heme degradation products.
Purpose of the Study:
- To investigate the role of Heme oxygenases (HO) in the atherosclerotic process.
- To determine if HO-1 induction attenuates monocyte chemotaxis induced by oxidized LDL.
- To evaluate the anti-atherogenic effects of modulating HO activity in animal models.
Main Methods:
- Investigated HO-1 induction in human aortic endothelial and smooth muscle cell cocultures exposed to oxidized LDL.
- Confirmed HO-1 expression in human, murine, and rabbit atherosclerotic lesions.
- Modulated HO activity in LDL-receptor knockout mice and Watanabe heritable hyperlipidemic rabbits to assess anti-atherogenic effects.
Main Results:
- Mildly oxidized LDL markedly induced HO-1 in vascular cells.
- HO-1 induction attenuated monocyte chemotaxis.
- HO activity modulation demonstrated anti-atherogenic properties, with reduced lesion formation.
- HO expression inversely correlated with lipid peroxide levels and influenced the nitric oxide pathway.
Conclusions:
- Heme oxygenases (HO), particularly HO-1, are induced during the atherosclerotic process.
- HO functions as an intrinsic protective pathway within the vascular wall against atherosclerosis.
- HO activity may represent a therapeutic target for ischemic cardiovascular disease.
Abstract:
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.