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. 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. 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.

Plasmacytoid Dendritic Cells Play a Key Role in Promoting Atherosclerosis in Apolipoprotein E-Deficient Mice / N., Macritchie; Grassia, Gianluca; S. R., Sabir; Maddaluno, Marcella; P., Welsh; N., Sattar; Ialenti, Armando; M., Kurowska Stolarska; I. B., Mcinnes; J. M., Brewer; P., Garside; Maffia, Pasquale. - In: ARTERIOSCLEROSIS, THROMBOSIS, AND VASCULAR BIOLOGY. - ISSN 1079-5642. - 32:(2012), pp. 2569-2579. [10.1161/ATVBAHA.112.251314]

Plasmacytoid Dendritic Cells Play a Key Role in Promoting Atherosclerosis in Apolipoprotein E-Deficient Mice

GRASSIA, GIANLUCA;MADDALUNO, MARCELLA;IALENTI, ARMANDO;MAFFIA, PASQUALE
2012

Abstract

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. 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. 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.
2012
Plasmacytoid Dendritic Cells Play a Key Role in Promoting Atherosclerosis in Apolipoprotein E-Deficient Mice / N., Macritchie; Grassia, Gianluca; S. R., Sabir; Maddaluno, Marcella; P., Welsh; N., Sattar; Ialenti, Armando; M., Kurowska Stolarska; I. B., Mcinnes; J. M., Brewer; P., Garside; Maffia, Pasquale. - In: ARTERIOSCLEROSIS, THROMBOSIS, AND VASCULAR BIOLOGY. - ISSN 1079-5642. - 32:(2012), pp. 2569-2579. [10.1161/ATVBAHA.112.251314]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/509061
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