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Increased levels of CCR7 ligands in carotid atherosclerosis: different effects in macrophages and smooth muscle cells

Item Type:Article
Title:Increased levels of CCR7 ligands in carotid atherosclerosis: different effects in macrophages and smooth muscle cells
Creators Name:Halvorsen, B. and Dahl, T.B. and Smedbakken, L.M. and Singh, A. and Michelsen, A.E. and Skjelland, M. and Krohg-Sørensen, K. and Russell, D. and Höpken, U.E. and Lipp, M. and Damås, J.K. and Holm, S. and Yndestad, A. and Biessen, E.A. and Aukrust, P.
Abstract:AIM: The homeostatic chemokines CCL19 and CCL21 and their receptor CCR7 have recently been linked to atherogenesis. We investigated the expression of CCL19/CCL21/CCR7 in carotid atherosclerosis as well as the ability of these chemokines to modulate lipid accumulation in macrophages and vascular smooth muscle cell (SMC) phenotype.Methods and ResultsOur major findings were: (i) Patients with carotid atherosclerosis (n=158) had increased plasma levels of CCL21, but not of CCL19, compared to controls (n=20), with particularly high levels in symptomatic (n=99) as compared with asymptomatic (n=59) disease. (ii) Carotid plaques showed markedly increased mRNA levels of CCL21 and CCL19 in symptomatic (n=14) as compared with asymptomatic (n=7) patients, with CCR7 localized to macrophages and vascular SMC (immunohistochemistry). (iii) In vitro, CCL21, but not CCL19, increased the binding of modified LDL and promoted lipid accumulation in THP-1 macrophages. (iv). CCL19, but not CCL21, increased proliferation and release and activity of matrix metalloproteinase (MMP) 1 in vascular SMC. (v). The differential effects of CCL19 and CCL21 in macrophages and SMC seem to be attributable to divergent signaling pathways, with CCL19-mediated activation of AKT in SMC and CCL21-mediated activation of extracellular signal-regulated kinase 1/2 in macrophages. CONCLUSION: CCL19 and CCL21 are up-regulated in carotid atherosclerosis. The ability of CCL21 to promote lipid accumulation in macrophages and of CCL19 to induce proliferation and MMP-1 expression in vascular SMC could contribute to their pro-atherogenic potential.
Keywords:Atherosclerosis, Inflammation, Chemokines, SMC, Macrophages
Source:Cardiovascular Research
ISSN:0008-6363
Publisher:Oxford University Press (U.K.)
Volume:102
Number:1
Page Range:148-156
Date:1 April 2014
Official Publication:https://doi.org/10.1093/cvr/cvu036
PubMed:View item in PubMed

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