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Estrogen activates endothelial exocytosis

Title
Estrogen activates endothelial exocytosis
Authors
Kim, Christine S.Yea, KyungmooMorrell, Craig N.Jeong, YoungtaeLowenstein, Charles J.
DGIST Authors
Kim, Christine S.; Yea, Kyungmoo; Morrell, Craig N.; Jeong, Youngtae; Lowenstein, Charles J.
Issue Date
2021-06
Citation
Biochemical and Biophysical Research Communications, 558, 29-35
Type
Article
Author Keywords
EstrogenExocytosisEndothelial cellsPlateletThromboembolism
Keywords
NITRIC-OXIDE SYNTHASEVENOUS THROMBOEMBOLISMHORMONE-THERAPYPLUS PROGESTINRECEPTORESTRADIOLASSOCIATIONHEARTRISK17-BETA-ESTRADIOL
ISSN
0006-291X
Abstract
Estrogen therapy is used to treat patients with post-menopausal symptoms, such as hot flashes and dyspareunia. Estrogen therapy also decreases the risk of fractures from osteoporosis in post-menopausal women. However, estrogen increases the risk of venous thromboembolic events, such as pulmonary embolism, but the pathways through which estrogen increase the risk of thromboembolism is unknown. Here, we show that estrogen elicits endothelial exocytosis, the key step in vascular thrombosis and inflammation. Exogenous 17β-estradiol (E2) stimulated endothelial exocytosis of Weibel-Palade bodies (WPBs), releasing von Willebrand factor (vWF) and interleukin-8 (IL-8). Conversely, the estrogen antagonist ICI-182,780 interfered with E2-induced endothelial exocytosis. The ERα agonist propyl pyrazole triol (PPT) but not the ERβ agonist diarylpropionitrile (DPN) induced vWF release, while ERα silencing counteracted vWF release by E2, suggesting that ERα mediates this effect. Exocytosis triggered by E2 occurred rapidly within 15 min and was not inhibited by either actinomycin D or cycloheximide. On the contrary, it was inhibited by the pre-treatment of U0126 or SB203580, an ERK or a p38 inhibitor, respectively, suggesting that E2-induced endothelial exocytosis is non-genomically mediated by the MAP kinase pathway. Finally, E2 treatment enhanced platelet adhesion to endothelial cells ex vivo, which was interfered with the pre-treatment of ICI-182,780 or U0126. Taken together, our data show that estrogen activates endothelial exocytosis non-genomically through the ERα-MAP kinase pathway. Our data suggest that adverse cardiovascular effects such as vascular inflammation and thrombosis should be considered in patients before menopausal hormone treatment. © 2021 Elsevier Inc.
URI
http://hdl.handle.net/20.500.11750/13760
DOI
10.1016/j.bbrc.2021.04.019
Publisher
Elsevier B.V.
Related Researcher
  • Author Yea, Kyungmoo Protein Engineering Lab
  • Research Interests Antibody, Engineering, Phage Display, Therapeutics, Immune, Exosome, Translational, Cytokine
Files:
There are no files associated with this item.
Collection:
Department of New BiologyProtein Engineering Lab1. Journal Articles
Department of New BiologyLab of Stem Cell Biology & Cancer Precision Medicine1. Journal Articles


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