Abstract
Cysteinyl leukotrienes (cys‐LTs) include leukotriene (LT) C4, LTD4, LTE4 are potent inflammatory lipid mediators that have been recently implicated in atherosclerosis. However, the molecular mechanisms by which cys‐LTs mediate atherosclerosis are not known. In the present study, we investigated the role of cys‐LTs in the regulation of endothelial functions and its contribution to the progression of atherosclerosis. We found that human endothelial cells (HUVECs) express cys‐LT receptors, CysLT1R and CysLT2R, with the expression of CysLT2R higher than CysLT1R. Interestingly, we found that activation of both CysLTRs induced calcium influx, ERK phosphorylation and cell proliferation in endothelial cells as measured by calcium imaging, western blotting and XTT assay, respectively. Importantly, LTD4 induced robust endothelial cell contraction and barrier dysfunction in endothelial monolayer. Finally, treatment of HUVECs with LTD4 induced the expression of inflammatory cell adhesion receptors such as ICAM1, VCAM and P‐selectin on endothelial monolayer with concomitant increase in HL‐60 cell attachment which is the hallmark of atherosclerosis. Taken together, our results suggest that cys‐LTs‐induce atherosclerosis by activating vascular endothelial cell inflammatory phenotype.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
