Functional Heterogeneity of Vascular Endothelial Cells
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Pharmacology
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This review has highlighted some of the well-described differences in endothelial cells derived from different sites of the vascular tree. In presenting a select group of endothelial properties, there was no intention to imply that these are the only properties of endothelial cells that exhibit heterogeneity. Nonetheless, having described endothelial heterogeneity in regard to a number of defined properties, we are left with persistent questions including: Are these divergent properties of endothelial cells fixed? Alternatively, can we alter the properties of endothelial cells by affecting the signals from the environment? A number of reports strongly suggest that endothelial cells are capable of acquiring new properties. Stewart and Wiley investigated the role of the neural tissue environment on the differentiation of brain capillary endothelial cells. These authors transplanted ectopic sites, i.e. vascular segments of brain from very young quail embryos to chick coeliac cavity, and a quail somites to chick brain ventricles. The distinctive morphology of quail cells provided a cell marker to differentiate host from graft. The results of this study demonstrated that mesenteric or somatic vessels growing into grafted brain developed functional, structural and histochemical features specific for neural capillaries. Conversely, capillaries in mesodermal tissue that had been grafted to the brain were devoid of the neural capillary characteristics, indicating that brain vessels do not form a barrier when they are made to vascularize non-neural tissue. Milici and Carley reported that bovine adrenal capillary cells cultured on plastic exhibited occasional diaphragmed fenestrations and no transendothelial channels. However, if these same cells were cultured on a basement membrane (matrix) laid down by MDCK cells (a canine nephron epithelial cell line), the cells responded by increasing the number of diaphragmed fenestrations and transendothelial channels. This cell culture study supported an earlier whole animal study in which the importance of the epithelium and/or epithelial basal lamina in the maintenance of endothelial ultrastructure was demonstrated in a developmental study of rat intestinal capillaries. In this earlier study, it was noted that epithelial development coincided with the formation of fenestrations by the endothelium. Enzymatic activities of endothelial cells can also be altered by environmental signals. For example, primary cerebral microvascular endothelial cells exhibit barrier features and are enriched in gamma-glutamyl transpeptidase activity, yet rapidly lose the activity when subcultured.(ABSTRACT TRUNCATED AT 400 WORDS)
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