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Connexins in endothelial barrier function – novel therapeutic targets countering vascular hyperpermeability

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
Topic:

Theme Issue
Heparin-induced thrombocytopenia in 2017 and beyond

DOI: https://doi.org/10.1160/TH16-03-0210
Issue: 2016: 116/5 (Nov) pp. 777-1002
Pages: 852-867
Ahead of Print: 2016-08-04

Connexins in endothelial barrier function – novel therapeutic targets countering vascular hyperpermeability

A. S. C. Soon (1), J. W. Chua (1, 2), D. L. Becker (1, 3)

(1) Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; (2) Nanyang Institute of Technology in Health and Medicine, Interdisciplinary Graduate School, Nanyang Technological University, Singapore; (3) Institute of Medical Biology, A*Star, Immunos, Biomedical Grove, Singapore

Keywords

endothelial cells, permeability, Connexins, gap junctions

Summary

Prolonged vascular hyperpermeability is a common feature of many diseases. Vascular hyperpermeability is typically associated with changes in the expression patterns of adherens and tight junction proteins. Here, we focus on the less-appreciated contribution of gap junction proteins (connexins) to basal vascular permeability and endothelial dysfunction. First, we assess the association of connexins with endothelial barrier integrity by introducing tools used in connexin biology and relating the findings to customary readouts in vascular biology. Second, we explore potential mechanistic ties between connexins and junction regulation. Third, we review the role of connexins in microvascular organisation and development, focusing on interactions of the endothelium with mural cells and tissue-specific perivascular cells. Last, we see how connexins contribute to the interactions between the endothelium and components of the immune system, by using neutrophils as an example. Mounting evidence of crosstalk between connexins and other junction proteins suggests that we rethink the way in which different junction components contribute to endothelial barrier function. Given the multiple points of connexin-mediated communication arising from the endothelium, there is great potential for synergism between connexin-targeted inhibitors and existing immune-targeted therapeutics. As more drugs targeting connexins progress through clinical trials, it is hoped that some might prove effective at countering vascular hyperpermeability.

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