The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Connexin37 protects against atherosclerosis by regulating monocyte adhesion
Open accessAbstract
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.
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Cites
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Self-citationBeyond the gap: functions of unpaired connexon channels
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Self-citationNucleotide receptors: an emerging family of regulatory molecules in blood cells
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Prediction of the Risk of Myocardial Infarction from Polymorphisms in Candidate Genes
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Sessile alveolar macrophages communicate with alveolar epithelium to modulate immunity
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Self-citationMechanisms of ATP Release by Inflammatory Cells
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Role of the Connexin C-terminus in skin pattern formation of Zebrafish
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Metadata
- Authors
- Wong, C. W., Christen, T., Roth, I., Chadjichristos, C. E., Derouette, J.-P., Foglia, B. F., Chanson, M., Goodenough, D. A., & Kwak, B. R.
- Venue
- Nature Medicine
- Published
- 2006-07-23
- Volume
- 12
- Issue
- 8
- Pages
- 950-954
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W1965834069
- Cited by
- 273
- References
- 27
- FWCI
- 7.37
- Type
- journal article
- Language
- en
- Open access
- green
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