In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 38, No. Suppl_1 ( 2018-05)
Abstract:
Atherosclerosis is a chronic sterile inflammation of the vascular wall triggered by hyperlipidemia. The role of dendritic cells (DCs) in the development of atherosclerosis has not been recognised until the last decade. DCs can engulf lipids to adopt a foam cell-like appearance that may constitute the earliest stages of plaque formation. DCs may also recruit T cells to the inflamed vessel wall via secretion of chemokines and stimulate T cell responses via cytokines. PPARD is a nuclear receptor, which acts as a sensor of native and oxidized fatty acids. We examined whether PPARD regulates DC function in response to hyperlipidemia and affect atherosclerotic lesion growth. We used Ppard fl/fl mice and Itgax-cre (CD11c-Cre) mice crossed with Apoe -/- mice to generate Ppard f/f ;CD11c Cre/+ ;Apoe -/- as DC-specific knockout of PPARD on Apoe-KO background (Ppard DC-KO ) and Ppard f/f ;Apoe -/- (Ppard DC-WT ) as controls. Ppard DC-KO and Ppard DC-WT were fed with high cholesterol diet for 4 months. Tissues were dissected and digested to obtain single cell suspension for flow cytometric analysis. Bone marrow derived DCs were isolated and cultured in RPMI with serum and GM-CSF and maturated with LPS.Atherosclerotic lesion size and collagen deposition decreased in Ppard DC-KO mice. Less CD4 and CD8 T lymphocytes were found in the atherosclerotic lesion of Ppard DC-KO mice comparing to Ppard DC-WT mice. Ppard deletion in DCs reduced DC infiltration especially CD11b + CD103 - DCs in the atherosclerotic lesion. Production of IFNγ from CD4 + T cells decreased in Ppard DC-KO mice. In BMDCs from Ppard DC-KO mice, LPS and palmitic acid induced expression of co-stimulatory molecules CD80 and CD86, as well as TNF were decreased. LDL uptake was attenuated in BMDCs from PpardDC-KO mice. Our results suggested that PPARD may be involved in DC mediated T cell activation in response to hyperlipidemia. Deletion of PPARD in DCs attenuated plaque formation in atherosclerosis. Whether lipid sensing and uptake by PPARD is required for the enhanced inflammatory response in atherosclerotic mice requires further study. (This study is supported by Hong Kong Health Bureau HMRF 05162906 and 01150057, Hong Kong RGC T402/13-N and CRF C4024-16W, and CUHK Direct grants)
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/atvb.38.suppl_1.186
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2018
detail.hit.zdb_id:
1494427-3
