Endothelial barrier function is differentially regulated by CEACAM1-mediated signaling

What is it about?

Endothelial barrier regulation represents a key process for the balance and maintenance of vascular homeostasis. The cell adhesion molecule CEACAM1 has been shown to be involved in vasculogenesis, angiogenesis and lymphangiogenesis. Furthermore, CEACAM1-deficient mice were reported to exhibit increased vascular permeability and to develop small atherosclerotic lesions that point to the involvement of CEACAM1 in endothelial barrier regulation. However, the role of CEACAM1 in the homeostasis of mature vessels and its targets therein are largely unknown. Here, we show that CEACAM1 differentially regulates main aspects of endothelial signaling and barrier function. CEACAM1 deficiency affects vascular nitric oxide bioavailability by targeting sub-cellular localization of eNOS, it increases leukocyte-endothelial interaction by impairment of endothelial glycocalyx and it age-dependently modulates endothelial barrier function. Thus, CEACAM1 deficiency induces endothelial dysfunction that is considered to be an early step towards atherosclerosis and myocardial infarction. While the present data are obtained from vascular studies and provide mechanistic insights into CEACAM1 role in endothelial barrier one should consider that the demonstrated mechanisms might also apply to numerous epithelia expressing CEACAM1 at their luminal surface and thus are of broad relevance.

Featured Image