Estradiol regulates expression of polysialated neural cell adhesion molecule by human vascular endothelial cells.
BACKGROUND
The mechanism of atherogenesis includes leukocyte adhesion to endothelial cells followed by migration into the subendothelial space. The polysialylated neural cell adhesion molecules (PSA-nCAMs) are a group of hydrophilic neural cell adhesion molecule (NCAM) isoforms that inhibit NCAM: NCAM association, thereby blocking cell: cell adhesion. During previous studies, we demonstrated that sialylation of specific NCAMs are upregulated at proestrus in the rat and that PSA-nCAM is expressed by the rat vascular endothelium.


RESULTS
In this study, we sought the presence of PSA-nCAM in human vessels and regulation of its expression in estradiol-treated human umbilical vascular endothelial cells (HUVEC). Immunoreactive PSA-nCAM (ir-PSA-nCAM) was shown in blood and lymph vessels of adult rats and human brain, skin, liver, lung, cervix, endometrium, and ovary. Staining for ir-PSA-nCAM was present on the glycocalyceal surface of estradiol-treated HUVEC, but not in the presence of the estrogen receptor (ER)-blocker fulvestrant. Western blotting confirmed these findings.


CONCLUSIONS
PSA-nCAM is widely present in the glycocalyx of human and rat vascular endothelium. It also is expressed by HUVEC, in which it is induced by estradiol. The estrogen-regulated presence of vascular PSA-nCAM could diminish NCAM-dependent interactions between vessels and circulating leukocytes, thereby impeding vascular inflammation and atherogenesis, and, contributing to estrogen-induced cardioprotection. This hypothesized action is presently under study.
Park
Hyein
H
Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY, USA.
Pagan
Lisandra
L
Tan
Orkun
O
Fadiel
Ahmed
A
Demir
Necdet
N
Huang
Kui
K
Mittal
Khushbakhat
K
Naftolin
Frederick
F
D000818:Animals; D001808:Blood Vessels / Q000737:chemistry; D001923:Brain Chemistry; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000737:chemistry; D004717:Endometrium / Q000737:chemistry; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008099:Liver / Q000737:chemistry; D008168:Lung / Q000737:chemistry; D042601:Lymphatic Vessels / Q000737:chemistry; D039842:Neural Cell Adhesion Molecule L1 / Q000032:analysis / Q000235:genetics*; D010053:Ovary / Q000737:chemistry; D051381:Rats; D012794:Sialic Acids / Q000032:analysis / Q000235:genetics*; D012867:Skin / Q000737:chemistry; D014471:Umbilical Veins
D004965:Estrogen Antagonists; D039842:Neural Cell Adhesion Molecule L1; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule; D000077267:Fulvestrant; D004958:Estradiol