Leukotriene B signaling through NF κB dependent BLT…白三烯信号通过κ依赖性.pdfVIP

Leukotriene B4 signaling through NF-B-dependent BLT1 receptors on vascular smooth muscle cells in atherosclerosis and intimal hyperplasia ¨ † † ¨ ¨ ‡ † † ¨ †§ Magnus Back* , De-xiu Bu* , Robert Branstrom , Yuri Sheikine* , Zhong-Qun Yan* , and Goran K. Hansson* Departments of *Medicine and ‡Surgical Sciences, Karolinska Institutet, and †Center for Molecular Medicine, Karolinska University Hospital, SE-171 76 Stockholm, Sweden Edited by Louis J. Ignarro, University of California School of Medicine, Los Angeles, CA, and approved October 5, 2005 (received for review July 12, 2005) Leukotriene B (LTB ), a potent leukocyte chemoattractant derived sclerotic mice strains with the BLT receptor antagonist 4 4 1 from the 5-lipoxygenase metabolism of arachidonic acid, exerts its CP105696 for 35 days reduces atherosclerotic lesion area and action by means of specific cell surface receptors, denoted BLT1 and lipid accumulation significantly (16), whereas ApoE-deficient BLT . In this study, BLT receptor proteins were detected in human 2 1 mice crossed with BLT1 receptor-deficient mice display reduced carotid artery atherosclerotic plaques, colocalizing with markers lesion formation only during early stages of disease (4 and 8 for macrophages, endothelial cells, and vascular smooth muscle weeks) (17). Also, studies of 5-LO-deficient atherosclerotic cells (SMC). Challenge of human coronary artery SMC with either mouse strains are contradictory, with both a reduction of LTB4 o