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Heme oxygenase-1 expression in macrophages plays a beneficial role in atherosclerosis.
- Source :
-
Circulation research [Circ Res] 2007 Jun 22; Vol. 100 (12), pp. 1703-11. Date of Electronic Publication: 2007 May 10. - Publication Year :
- 2007
-
Abstract
- Heme oxygenase (HO-1) is the rate-limiting enzyme in the catabolism of heme, which leads to the generation of biliverdin, iron, and carbon monoxide. It has been shown to have important antioxidant and antiinflammatory properties that result in a vascular antiatherogenic effect. To determine whether HO-1 expression in macrophages constitutes a significant component of the protective role in atherosclerosis, we evaluated the effect of decreased or absent HO-1 expression in peritoneal macrophages on oxidative stress and inflammation in vitro, and the effect of complete deficiency of HO-1 expression in macrophages in atherosclerotic lesion formation in vivo. We found that compared with HO-1(+/+) controls, peritoneal macrophages from HO-1(-/-) and HO-1(+/-) mice exhibited (1) increased reactive oxygen species (ROS) generation, (2) increased proinflammatory cytokines such as monocyte chemotactic protein 1 (MCP-1) and interleukin 6 (IL-6), and (3) increased foam cell formation when treated with oxLDL, attributable in part to increased expression of scavenger receptor A (SR-A). Bone marrow transplantation experiments performed in lethally irradiated LDL-R null female mice, reconstituted with bone marrow from HO-1(-/-) versus HO-1(+/+) mice, revealed that HO-1(-/-) reconstituted animals exhibited atherosclerotic lesions with a greater macrophage content as evaluated by immunohistochemistry and planimetric assessment. We conclude that HO-1 expression in macrophages constitutes an important component of the antiatherogenic effect by increasing antioxidant protection and decreasing the inflammatory component of atherosclerotic lesions.
- Subjects :
- Animals
Antioxidants metabolism
Atherosclerosis pathology
Bone Marrow Transplantation pathology
Chemokine CCL2 metabolism
Foam Cells pathology
Gene Expression Regulation
Gene Expression Regulation, Enzymologic
Interleukin-6 metabolism
Macrophages pathology
Mice
Oxidative Stress physiology
Reactive Oxygen Species metabolism
Receptors, LDL genetics
Receptors, LDL physiology
Scavenger Receptors, Class A genetics
Scavenger Receptors, Class A physiology
Atherosclerosis metabolism
Atherosclerosis prevention & control
Heme Oxygenase-1 metabolism
Macrophages enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4571
- Volume :
- 100
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Circulation research
- Publication Type :
- Academic Journal
- Accession number :
- 17495224
- Full Text :
- https://doi.org/10.1161/CIRCRESAHA.107.151720