期刊
ATHEROSCLEROSIS
卷 203, 期 2, 页码 395-400出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2008.07.045
关键词
Leukotriene; Atherosclerosis; Inflammation; Macrophage
资金
- Canadian Institutes of Health Research [MOP-67146]
- German Research Organization [HA1083/15-1/HA1083/13-3]
- Merck and Co. [L739,010]
The 5-lipoxygenase (5-LO) catalyzed formation of leukotriene (LT) lipid mediators is a pathway contributing to inflammatory events ill asthma and more recently has been associated with cardiovascular disease. However, the relative impact of this pathway in atherogenesis has been controversial and a variety of mixed results reported. The goal of these Studies was to assess the importance of the 5-LO/LT pathway in mice with either genetic (5-LO-/-) or pharmacological (L-739,010) inhibition of the 5-LO pathway oil an apolipoprotein E deficient (apoE(-/-)) background when Subjected to either an 8-week (Paigen) or 6 months (Western) atherosclerotic diet regimen. Atherosclerotic lesion analysis at the aortic root, brachiocephalic artery and throughout the whole aorta by en face Sudan IV staining was determined, as well as blood lipid levels. Ex vivo calcium ionophore-stimulation of whole blood demonstrated a significant reduction in the capacity to form LTB4 in 5-LO-/- and drug-treated 5-LO+/+ mice. Quantitative analysis of atherosclerotic lesions did not differ between groups at all three sites. Moreover, the composition of advanced lesions in the brachiocephalic arteries did not indicate altered plaque disruption as a result of 5-LO gene inactivation. These result was do not support a role for the 5-LO/LT pathway in intermediate to advanced atherosclerotic lesion development in mice. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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