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Inflammatory Role of Cysteinyl Leukotrienes in Human Vascular Endothelial Cells
Author(s) -
Duah Ernest,
Kondeti Vinay,
Adapala Ravi K,
Sanford Joel,
Thodeti Charles K,
Paruchuri Sailaja
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.813.12
Subject(s) - endothelial stem cell , microbiology and biotechnology , chemistry , receptor , leukotriene , inflammation , cell , cell adhesion , endothelial dysfunction , cancer research , biology , immunology , biochemistry , endocrinology , in vitro , asthma
Cysteinyl leukotrienes (cys‐LTs) include leukotriene (LT) C 4 , LTD 4 , LTE 4 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, CysLT 1 R and CysLT 2 R, with the expression of CysLT 2 R higher than CysLT 1 R. 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, LTD 4 induced robust endothelial cell contraction and barrier dysfunction in endothelial monolayer. Finally, treatment of HUVECs with LTD 4 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.