Smooth Muscle Cells in Human Atherosclerotic Plaques Express the Fractalkine Receptor CX ₃ CR1 and Undergo Chemotaxis to the CX ₃ C Chemokine Fractalkine (CX ₃ CL1)

Abstract

Background-Chemokines are important mediators of inflammatory cell recruitment that play a significant role in atherosclerosis. Fractalkine (CX 3 CL1) is an unusual membrane-bound chemokine that mediates chemotaxis through the CX 3 CR1 receptor. Recently, functional polymorphisms in the human CX3CR1 gene have been described that are associated with coronary artery disease. Methods and Results-We investigated the expression of the CX 3 C chemokine fractalkine and its receptor CX 3 CR1 in human coronary artery plaques by immunocytometry. We show that a subset of mononuclear cells expresses high levels of fractalkine in human coronary atherosclerotic plaques and that smooth muscle cells within the neointima express the fractalkine receptor CX 3 CR1. There is a positive correlation between the number of fractalkine-expressing cells and the number of CX 3 CR1-positive cells in human atherosclerotic plaques (rϭ0.70, nϭ15 plaques). Furthermore, we demonstrate that cultured vascular smooth muscle cells express the CX 3 CR1 receptor and undergo chemotaxis to fractalkine that can be inhibited by G protein inactivation by pertussis toxin. Conclusions-These results suggest that in human atherosclerosis, fractalkine, rather than mediating inflammatory cell recruitment, can act as a mediator of smooth muscle cell migration.

CX 3 CR1 Deficiency Confers Protection From Intimal Hyperplasia After Arterial Injury

“…20 Monocyte adhesion and arrest on neointimal SMC is dependent on CX 3 CL1, 21 and VSMCs undergo chemotaxis toward CX 3 CL1. 17 Thus, CX 3 CL1 may act not only on monocytes, but also may function to stimulate SMC proliferation and recruitment into the neointima.In the present study, we employed an endoluminal arterial injury model to investigate the role of CX 3 CR1 in the pathogenesis of vascular injury. This model elicits a stereotypic response that allows for assessment of the functional roles of platelets, monocytes, and VSMCs.…”

Fractalkine mediates T cell–dependent proliferation of synovial fibroblasts in rheumatoid arthritis

“…Reports by Lucas et al (33) have indicated that aortic smooth muscle cells, another type of specialized mesenchymal cells, utilize the CX 3 CR1-FKN pathway for proliferation control. In vitro, the soluble form of FKN promotes aortic smooth muscle cell proliferation through NF-B signaling (34).…”

Transmembrane chemokines: Versatile ‘special agents’ in vascular inflammation

“…Within the vasculars ystem CX3CL1 has beenl ocated on endothelial cells and smoothm uscle cells (SMCs) in situ (33). CX3CL1and CXCL16 were found to be induced in both celltypes in vitro upon activation with proinflamatorymediators(reviewed in [34]).…”

“…Atherosclerosis is characterized by increased infiltration of leukocytesinparticularmonocytic cells in the vascular wall. Intimalm acrophages within atherosclerotic lesions have beenfound to express CX3CL1 and CXCL16 (33,(42)(43)(44)89). CX3CL1 is also profoundlye xpressed by SMCs in the media of humancoronary arteries (33).…”

“…Intimalm acrophages within atherosclerotic lesions have beenfound to express CX3CL1 and CXCL16 (33,(42)(43)(44)89). CX3CL1 is also profoundlye xpressed by SMCs in the media of humancoronary arteries (33). Theincreased expression of the transmembrane chemokines is associated with an increased presenceo fr eceptor-positive monocytesa nd Tc ells within the vascularlesion.…”