Connexin37 protects against atherosclerosis by regulating monocyte adhesion

Wong, Cindy W; Christen, Thomas; Roth, Isabelle; Chadjichristos, Christos E; Derouette, Jean-Paul; Foglia, Bernard F; Chanson, Marc; Goodenough, Daniel A; Kwak, Brenda R (2006). Connexin37 protects against atherosclerosis by regulating monocyte adhesion. Nature medicine, 12(8), pp. 950-4. New York, N.Y.: Nature Publishing Group 10.1038/nm1441

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A genetic polymorphism in the human gene encoding connexin37 (CX37, encoded by GJA4, also known as CX37) has been reported as a potential prognostic marker for atherosclerosis. The expression of this gap-junction protein is altered in mouse and human atherosclerotic lesions: it disappears from the endothelium of advanced plaques but is detected in macrophages recruited to the lesions. The role of CX37 in atherogenesis, however, remains unknown. Here we have investigated the effect of deleting the mouse connexin37 (Cx37) gene (Gja4, also known as Cx37) on atherosclerosis in apolipoprotein E-deficient (Apoe(-/-)) mice, an animal model of this disease. We find that Gja4(-/-)Apoe(-/-) mice develop more aortic lesions than Gja4(+/+)Apoe(-/-) mice that express Cx37. Using in vivo adoptive transfer, we show that monocyte and macrophage recruitment is enhanced by eliminating expression of Cx37 in these leukocytes but not by eliminating its expression in the endothelium. We further show that Cx37 hemichannel activity in primary monocytes, macrophages and a macrophage cell line (H36.12j) inhibits leukocyte adhesion. This antiadhesive effect is mediated by release of ATP into the extracellular space. Thus, Cx37 hemichannels may control initiation of the development of atherosclerotic plaques by regulating monocyte adhesion. H36.12j macrophages expressing either of the two CX37 proteins encoded by a polymorphism in the human GJA4 gene show differential ATP-dependent adhesion. These results provide a potential mechanism by which a polymorphism in CX37 protects against atherosclerosis.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Physiology

UniBE Contributor:

Derouette, Jean-Paul

ISSN:

1078-8956

ISBN:

16862155

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:45

Last Modified:

17 Mar 2015 21:43

Publisher DOI:

10.1038/nm1441

PubMed ID:

16862155

Web of Science ID:

000239626200027

URI:

https://boris.unibe.ch/id/eprint/18539 (FactScience: 727)

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