Plasmacytoid dendritic cells play a key role in promoting atherosclerosis in apolipoprotein e-deficient mice

MacRitchie, N. et al. (2012) Plasmacytoid dendritic cells play a key role in promoting atherosclerosis in apolipoprotein e-deficient mice. Arteriosclerosis, Thrombosis, and Vascular Biology, 32(11), pp. 2569-2579. (doi:10.1161/ATVBAHA.112.251314)

MacRitchie, N. et al. (2012) Plasmacytoid dendritic cells play a key role in promoting atherosclerosis in apolipoprotein e-deficient mice. Arteriosclerosis, Thrombosis, and Vascular Biology, 32(11), pp. 2569-2579. (doi:10.1161/ATVBAHA.112.251314)

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Abstract

<p>Objective—Clinical studies have identified that reduced numbers of circulating plasmacytoid dendritic cells (pDCs) act as a predictor of cardiovascular events in coronary artery disease and that pDCs are detectable in the shoulder region of human atherosclerotic plaques, where rupture is most likely to occur. Results from animal models are controversial, with pDCs seen to inhibit or promote lesion development depending on the experimental settings. Here, we investigated the role of pDCs in atherosclerosis in apolipoprotein E−deficient mice.</p> <p>Methods and Results—We demonstrated that the aorta and spleen of both apolipoprotein E−deficient and C57BL/6 mice displayed similar numbers of pDCs, with similar activation status. In contrast, assessment of antigen uptake/presentation using the Eα/Y-Ae system revealed that aortic pDCs in apolipoprotein E−deficient- mice were capable of presenting in vivo systemically administered antigen. Continuous treatment of apolipoprotein E−deficient mice with anti−mouse plasmacytoid dendritic cell antigen 1 (mPDCA-1) antibody caused specific depletion of pDCs in the aorta and spleen and significantly reduced atherosclerosis formation in the aortic sinus (by 46%; P<0.001). Depletion of pDCs also reduced macrophages (by 34%; P<0.05) and increased collagen content (by 41%; P<0.05) in aortic plaques, implying a more stable plaque phenotype. Additionally, pDC depletion reduced splenic T-cell activation and inhibited interleukin-12, chemokine (C-X-C motif) ligand 1, monokine induced by interferon-γ, interferon γ−induced protein 10, and vascular endothelium growth factor serum levels.</p> <p>Conclusion—These results identify a critical role for pDCs in atherosclerosis and suggest a potential role for pDC targeting in the control of the pathology.</p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Maffia, Dr Pasquale and Welsh, Dr Paul and Garside, Professor Paul and Brewer, Professor James and MacRitchie, Mr Neil and Kurowska-Stolarska, Dr Mariola and Sattar, Professor Naveed
Authors: MacRitchie, N., Grassia, G., Sabir, S. R., Maddaluno, M., Welsh, P., Sattar, N., Ialenti, A., Kurowska-Stolarska, M., McInnes, I. B., Brewer, J. M., Garside, P., and Maffia, P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Arteriosclerosis, Thrombosis, and Vascular Biology
Publisher:American Heart Association
ISSN:1079-5642
ISSN (Online):1524-4636
Published Online:30 August 2012

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
404921Investigating the role of T cells in vascular pathologyPaul GarsideBritish Heart Foundation (BHF)PG/06/083/21198III -IMMUNOLOGY
524831Visualising antigen presentation in mouse models of atherosclerosisPasquale MaffiaMedical Research Scotland (MED-SCOT)276 FRGIII -IMMUNOLOGY