A novel endothelial-specific membrane protein is a marker of cell-cell contacts.

Abstract

Abstract. mAbs were raised in mice against cultured human endothelial cells (EC) and screened by indirect immunofluorescence for their ability to stain intercellular contacts. One mAb denoted 7B4 was identified which, out of many cultured cell types, specifically decorated cultured human EC. The antigen recognized by mAb 7B4 is bound at the appositional surfaces of cultured EC only as they become confluent and is stably expressed at intercellular boundaries of confluent monolayers. EC recognition specificity was maintained when the antibody was assayed by immunohistochemistry in tissue sections of many normal and malignant tissues and in blood vessels of different size and type. The antigen recognized by 7B4 was enriched at EC intercellular boundaries similarly in vitro and in situ. In vitro, addition of mAb 7B4 to confluent EC increased permeation of macromolecules across monolayers even without any obvious changes of cell morphology. In addition, when EC permeability was increased by agents such as thrombin, elastase, and TNF/~/IFN, its distribution pattern at intercellular contact rims was severely altered, mAb 7B4 immunoprecipitated a major protein of 140 kD from metabolicaUy and surface-labeled cultured EC extracts which appeared to be an integral membrane glycoprotein. On the basis of its distribution in cultured cells and in tissues in situ, 7B4 antigen is distinct from other described EC proteins enriched at intercellular contacts. NH2-terminal sequencing of the antigen, immunopurified from human placenta, and sequencing of peptides from tryptic peptide maps revealed identity to the cDNA deduced sequence of a recently identified new member of the cadherin family (Suzuki, S., K.Sano, and H. Tanihara. 1991. Cell Regul. 2:261-270.) These data indicate that 7134 antigen is an endothelialspecific cadherin that plays a role in the organization of lateral endothelial junctions and in the control of permeability properties of vascular endothelium.

Circulating endothelial progenitor cells, endothelial function, carotid intima–media thickness and circulating markers of endothelial dysfunction in people with type 1 diabetes without macrovascular disease or microalbuminuria

“…VEGFR-2 mediates most of the downstream angiogenic effects of VEGF, including microvascular permeability and endothelial cell proliferation, while VE-cadherin is specifically expressed in adherent junctions of endothelial cells and exerts important functions in cell-cell adhesion, thus promoting the integrity of the endothelium [20,21].…”

HIF-2α specifically activates the VE-cadherin promoter independently of hypoxia and in synergy with Ets-1 through two essential ETS-binding sites

“…Endothelial cells form the inner layer of all blood vessels, they express several molecular markers that characterize the endothelial phenotype, such as the VEGF receptor flk-1 (Millauer et al, 1993), the angiopoietin receptor Tie-2 (Sato et al, 1993;Schnu¨rch and Risau, 1993), VE-statin , or VE-cadherin (Lampugnani et al, 1992). VE-cadherin expression is mostly restricted to endothelial cells.…”

ETS1 lowers capillary endothelial cell density at confluence and induces the expression of VE-cadherin

“…VE-cadherin is a cell surface glycoprotein speci®-cally expressed by endothelial cells during mouse development and located at intercellular junctions in vivo and in vitro (Lampugnani et al, 1992;Breier et al, 1996). VE-cadherin regulates the growth of transfected CHO cells and is essential for the integrity of the endothelial monolayer (Navarro et al, 1995).…”