Journal
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Volume 23, Issue 8, Pages E37-E41Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.ATV.0000082689.46538.DF
Keywords
leukotrienes; endothelial cells; receptors; inflammation; arteriosclerosis
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Objective - The objective of the present study was to identify and characterize the cell-surface receptors on human umbilical vein endothelial cells (HUVECs) that transduce calcium transients elicited by cysteinyl leukotrienes (CysLTs), potent spasmogenic and proinflammatory agents with profound effects on the cardiovascular system. Methods and Results - Using quantitative reverse transcription - polymerase chain reaction, we found that HUVECs abundantly express CysLT(2)R mRNA in vast excess (> 4000-fold) of CysLT(1)R mRNA. Lipopolysaccharide, tumor necrosis factor-alpha, or interleukin-1beta caused a rapid ( within 30 minutes) and partially reversible suppression of CysLT2R mRNA levels. Challenge of HUVECs with BAY u9773, a specific CysLT(2)R agonist, triggered diagnostic Ca2+ transients. LTC4 and LTD4 are equipotent agonists, and their actions can be blocked by the dual-receptor antagonist BAY u9773, but not by the CysLT(1)R-selective antagonist MK571. Conclusions - HUVECs almost exclusively express the CysLT(2)R. Furthermore, Ca2+ fluxes elicited by CysLT in these cells emanate from perturbation of the CysLT(2)R, rather than the expected CysLT(1)R. Hence, signaling events involving CysLT(2)R might trigger functional responses involved in the critical components of LT-dependant vascular reactions, which in turn have implications for ischemic heart disease and myocardial infarction.
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