title: Estradiol regulates expression of polysialated neural cell adhesion molecule by human vascular endothelial cells.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY, USA.
authors.forename: Hyein
authors.initials: H
authors.lastname: Park
authors.forename: Lisandra
authors.initials: L
authors.lastname: Pagan
authors.forename: Orkun
authors.initials: O
authors.lastname: Tan
authors.forename: Ahmed
authors.initials: A
authors.lastname: Fadiel
authors.forename: Necdet
authors.initials: N
authors.lastname: Demir
authors.forename: Kui
authors.initials: K
authors.lastname: Huang
authors.forename: Khushbakhat
authors.initials: K
authors.lastname: Mittal
authors.forename: Frederick
authors.initials: F
authors.lastname: Naftolin
mesh_terms: 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
chemical_list: D004965:Estrogen Antagonists; D039842:Neural Cell Adhesion Molecule L1; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule; D000077267:Fulvestrant; D004958:Estradiol