Altered pattern of vascular connexin expression in atherosclerotic plaques.
Paracrine cell-to-cell interactions are crucial events during atherogenesis. However, little is known about the role of direct intercellular communication via gap junctions during this process. We have investigated the expression pattern of 3 vascular gap junction proteins (connexins) in mouse and human atherosclerotic plaques. Low density lipoprotein receptor-deficient mice were fed a high-fat diet for 0, 6, 10, or 14 weeks to induce different stages of atherosclerosis. Connexin37 (Cx37) and Cx40 were detected in the endothelium, and Cx43 was detected in the media of nondiseased aortas. In early atheromas, endothelial and medial connexin expression remained unchanged, and "islets" of Cx43 in smooth muscle cells and Cx37 in macrophages were observed in the neointima. In advanced atheromas, Cx37 was detected in medial smooth muscle cells and in macrophages in the lipid core but not in the endothelium covering the plaques. Cx40 could also no longer be detected in the endothelium covering the plaques. Cx43, on the other hand, was detected in the endothelium covering the shoulder of the plaques and also sparsely in neointimal smooth muscle cells. Similar results were obtained for human carotid arteries. In conclusion, vascular connexins are differentially expressed by atheroma-associated cells within lesions. These observations suggest a role for gap junctional intercellular communication during atherogenesis.
Kwak
Brenda R
BR
Division of Cardiology, Department of Medicine, University Hospital Geneva, Geneva, Switzerland.
Mulhaupt
Flore
F
Veillard
Niels
N
Gros
Daniel B
DB
Mach
François
F
D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism*; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D018031:Connexin 43 / Q000032:analysis*; D017630:Connexins / Q000032:analysis*; D018450:Disease Progression; D017629:Gap Junctions / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D011973:Receptors, LDL / Q000172:deficiency; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein
D002791:Cholesterol, Dietary; D018031:Connexin 43; D017630:Connexins; D011973:Receptors, LDL; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein