Format

Send to

Choose Destination
See comment in PubMed Commons below
Sci Rep. 2013 Nov 20;3:3274. doi: 10.1038/srep03274.

Cysteinyl leukotrienes regulate endothelial cell inflammatory and proliferative signals through CysLT₂ and CysLT₁ receptors.

Author information

1
Department of Chemistry, University of Akron, OH 44325.

Abstract

Cysteinyl leukotrienes (cys-LTs), LTC₄, LTD₄, LTE₄ are potent inflammatory lipid mediators that act through two distinct G-protein-coupled receptors, CysLT₁R and CysLT₂R. 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 (LTC₄ and LTD₄) induce robust calcium influx in human umbilical vein endothelial cells (HUVECs) through CysLT₂R, but not CysLT₁R. Further, cys-LT treatment induced endothelial cell (EC) contraction leading to monolayer disruption via CysLT₂R/Rho kinase dependent pathway. Furthermore, stimulation with cys-LTs potentiated TNFα-induced VCAM-1 expression and leukocyte recruitment to ECs through CysLT₂R. In contrast, we found that both LTC₄ and LTD₄ stimulated EC proliferation through CysLT₁R. Taken together, these results suggest that cys-LTs induce endothelial inflammation and proliferation via CysLT₂R/Rho kinase and CysLT₁R/Erk dependent pathways, respectively, which play critical role in the etiology of cardiovascular diseases such as atherosclerosis and myocardial infarction.

PMID:
24253666
PMCID:
PMC3834363
DOI:
10.1038/srep03274
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Support Center