Leukotriene Receptors Crucial Components in Vascular…白三烯受体血管中的关键组分.pdfVIP

Review Article Special Issue: Eicosanoid Receptors and Inflammation TheScientificWorldJOURNAL (2007) 7, 1422–1439 ISSN 1537-744X; DOI 10.1100/tsw.2007.187 Leukotriene Receptors: Crucial Components in Vascular Inflammation Magnus Bäck Department of Cardiology and Center for Molecular Medicine, Karolinska University Hospital, L8:03, 171 76 Stockholm, Sweden E-mail: Magnus.Back@ki.se Received January 22, 2007; Revised June 18, 2007; Accepted July 2, 2007; Published September 1, 2007 The accumulation of immune cells during vascular inflammation leads to formation of leukotrienes (LTs). While macrophages represent a major source of LT biosynthesis in the proximity of the vascular wall, activated T lymphocytes may, in addition, play a key regulatory role on macrophage expression of LT-forming enzymes. Within the vascular wall, LTs activate cell surface receptors of the BLT and CysLT subtypes expressed on vascular smooth muscle and endothelial cells. The LT receptor expression on those cells is highly dependent on transcriptional regulation by pro- and anti-inflammatory mediators. LT receptor activation on vascular smooth muscle cells is associated with both directly and indirectly induced vasoconstriction, as well as intimal hyperplasia through stimulation of migration and proliferation. On the other hand, endothelial LT receptors induce vasorelaxation and leukocyte recruitment and adhesion. Results from in vitro and in vivo studies of LT receptor antagonists indicate potential beneficial effects in atherosclerosis and other inflammatory cardiovascular diseases. KEYWORDS: atherosclerosis, eicosanoids, endothelium, intimal hyperplasia, leukotriene receptor antagonists, lipoxygenase, vascular smooth muscle cells INTRODUCTION Leukotriene Receptors Structural differences divi