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Cyclooxygenase-2 promotes early atherosclerotic lesion formation in ApoE-deficient and C57BL/6 mice
- Source :
-
Journal of Molecular & Cellular Cardiology . Sep2005, Vol. 39 Issue 3, p443-452. 10p. - Publication Year :
- 2005
-
Abstract
- Abstract: Cyclooxygenase (COX) 2 is expressed in atherosclerotic lesions. We have previously reported that selective inhibition of COX-2 reduces early atherosclerosis in LDLR deficient mice. To examine the role of COX-2 in atherosclerosis in other mouse models, we studied the effects of selective COX-2 inhibition (by rofecoxib and NS-398) and nonselective COX inhibition (by indomethacin) on early atherosclerotic lesion formation in apolipoprotein E-deficient (apoE–/–) mice. Selective COX-2 and nonselective COX inhibition reduced atherosclerosis in female apoE–/– mice by 35–38% and 38–51% in the proximal and en face aortas, respectively. Next we investigated the role of macrophage COX-2 by transplanting COX-2–/– fetal liver cells into C57BL/6 mice and challenging the mice with an atherogenic diet. Genetic deletion of COX-2 from hematopoietic cells reduced atherosclerosis by 51%. In addition, LPS activated COX-2–/– macrophages had decreased expression of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNFα). The results demonstrate that selective inhibition of COX-2 and elimination of COX-2 from macrophages significantly reduces early atherosclerotic lesion formation in apoE-deficient and C57BL/6 mice. These results are compatible with COX-2 expression by macrophages having a proatherogenic role, and support the potential of anti-inflammatory therapeutic approaches for atherosclerosis. [Copyright &y& Elsevier]
- Subjects :
- *APOLIPOPROTEIN E
*ATHEROSCLEROSIS
*BONE marrow
*INFLAMMATORY mediators
Subjects
Details
- Language :
- English
- ISSN :
- 00222828
- Volume :
- 39
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Journal of Molecular & Cellular Cardiology
- Publication Type :
- Academic Journal
- Accession number :
- 18236510
- Full Text :
- https://doi.org/10.1016/j.yjmcc.2005.06.011