title: Connexins in endothelial barrier function - novel therapeutic targets countering vascular hyperpermeability.
abstract: 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.
authors.forename: Allyson Shook Ching
authors.initials: AS
authors.lastname: Soon
authors.forename: Jia Wang
authors.initials: JW
authors.lastname: Chua
authors.affiliation: David L. Becker, PhD, Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, 308232 Singapore, Tel: +65 6592 3961, Fax: +65 6515 0417, E-mail: david.becker@ntu.edu.sg.
authors.forename: David Laurence
authors.initials: DL
authors.lastname: Becker
mesh_terms: D002199:Capillary Permeability; D017630:Connexins / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans
chemical_list: D017630:Connexins
keywords: Connexins; endothelial cells; gap junctions; permeability