Estradiol Regulates Expression of Polysialated Neural Cell Adhesion Molecule by Human Vascular Endothelial Cells

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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. 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. 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.