Macrophage apoAI protects against dyslipidemia-induced dermatitis and atherosclerosis without affecting HDL. J Lipid Res 2015 Mar;56(3):635-643
Date
01/17/2015Pubmed ID
25593328Pubmed Central ID
PMC4340310DOI
10.1194/jlr.M056408Scopus ID
2-s2.0-84925238577 (requires institutional sign-in at Scopus site) 24 CitationsAbstract
Tissue cholesterol accumulation, macrophage infiltration, and inflammation are features of atherosclerosis and some forms of dermatitis. HDL and its main protein, apoAI, are acceptors of excess cholesterol from macrophages; this process inhibits tissue inflammation. Recent epidemiologic and clinical trial evidence questions the role of HDL and its manipulation in cardiovascular disease. We investigated the effect of ectopic macrophage apoAI expression on atherosclerosis and dermatitis induced by the combination of hypercholesterolemia and absence of HDL in mice. Hematopoietic progenitor cells were transduced to express human apoAI and transplanted into lethally irradiated LDL receptor(-/-)/apoAI(-/-) mice, which were then placed on a high-fat diet for 16 weeks. Macrophage apoAI expression reduced aortic CD4(+) T-cell levels (-39.8%), lesion size (-25%), and necrotic core area (-31.6%), without affecting serum HDL or aortic macrophage levels. Macrophage apoAI reduced skin cholesterol by 39.8%, restored skin morphology, and reduced skin CD4(+) T-cell levels. Macrophage apoAI also reduced CD4(+) T-cell levels (-32.9%) in skin-draining lymph nodes but had no effect on other T cells, B cells, dendritic cells, or macrophages compared with control transplanted mice. Thus, macrophage apoAI expression protects against atherosclerosis and dermatitis by reducing cholesterol accumulation and regulating CD4(+) T-cell levels, without affecting serum HDL or tissue macrophage levels.
Author List
Tavori H, Su YR, Yancey PG, Giunzioni I, Wilhelm AJ, Blakemore JL, Zabalawi M, Linton MF, Sorci-Thomas MG, Fazio SAuthor
Mary Sorci Thomas PhD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsApolipoprotein A-I
Atherosclerosis
B-Lymphocytes
CD4-Positive T-Lymphocytes
Dendritic Cells
Dermatitis
Gene Expression Regulation
Humans
Hypercholesterolemia
Lipoproteins, HDL
Macrophages
Mice
Mice, Knockout