Cysteinyl leukotrienes regulate endothelial cell inflammatory and proliferative signals through CysLT? and CysLT? receptors.

ABSTRACT: Cysteinyl leukotrienes (cys-LTs), LTC?, LTD?, LTE? are potent inflammatory lipid mediators that act through two distinct G-protein-coupled receptors, CysLT?R and CysLT?R. Although cys-LTs are shown to induce vascular leakage and atherosclerosis, the molecular mechanism by which cys-LTs modulate endothelial function is not known. Here, we show that cys-LTs (LTC? and LTD?) induce robust calcium influx in human umbilical vein endothelial cells (HUVECs) through CysLT?R, but not CysLT?R. Further, cys-LT treatment induced endothelial cell (EC) contraction leading to monolayer disruption via CysLT?R/Rho kinase dependent pathway. Furthermore, stimulation with cys-LTs potentiated TNF?-induced VCAM-1 expression and leukocyte recruitment to ECs through CysLT?R. In contrast, we found that both LTC? and LTD? stimulated EC proliferation through CysLT?R. Taken together, these results suggest that cys-LTs induce endothelial inflammation and proliferation via CysLT?R/Rho kinase and CysLT?R/Erk dependent pathways, respectively, which play critical role in the etiology of cardiovascular diseases such as atherosclerosis and myocardial infarction.

SUBMITTER: Duah E 

PROVIDER: S-EPMC3834363 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature