Transcriptome Analysis Reveals Nonfoamy Rather Than Foamy Plaque Macrophages Are Proinflammatory in Atherosclerotic Murine Models

被引：321

作者：

Kim, Kyeongdae ^{[1
]}

Shim, Dahee ^{[1
]}

Lee, Jun Seong ^{[3
]}

Zaitsev, Konstantin ^{[7
,12
]}

Williams, Jesse W. ^{[7
]}

Kim, Ki-Wook ^{[7
]}

Jang, Man-Young ^{[1
]}

Jang, Hyung Seok ^{[1
]}

Yun, Tae Jin ^{[3
,8
]}

Lee, Seung Hyun ^{[1
]}

Yoon, Won Kee ^{[9
]}

Prat, Annik ^{[4
]}

Seidah, Nabil G. ^{[4
]}

Choi, Jungsoon ^{[2
]}

Lee, Seung-Pyo ^{[5
,6
]}

Yoon, Sang-Ho ^{[1
]}

Nam, Jin Wu ^{[1
]}

Seong, Je Kyung ^{[10
]}

Oh, Goo Taeg ^{[11
]}

Randolph, Gwendalyn J. ^{[7
]}

Artyomov, Maxim N. ^{[7
]}

Cheong, Cheolho ^{[3
,8
]}

Choi, Jae-Hoon ^{[1
]}

机构：

[1] Hanyang Univ, Res Inst Nat Sci, Dept Life Sci, Coll Nat Sci, Seoul, South Korea

[2] Hanyang Univ, Res Inst Nat Sci, Dept Math, Coll Nat Sci, Seoul, South Korea

[3] Inst Rech Clin Montreal, Lab Cellular Physiol & Immunol, Montreal, PQ, Canada

[4] Inst Rech Clin Montreal, Lab Biochem Neuroendocrinol, Montreal, PQ, Canada

[5] Seoul Natl Univ Hosp, Cardiovasc Ctr, Seoul, South Korea

[6] Seoul Natl Univ Hosp, Dept Internal Med, Seoul, South Korea

[7] Washington Univ, Sch Med, Dept Pathol & Immunol, 425 S Euclid Ave,Box 8118, St Louis, MO 63110 USA

[8] McGill Univ, Div Expt Med, Dept Med, Montreal, PQ, Canada

[9] KRIBB, Biomed Mouse Resource Ctr, Chungbuk, South Korea

[10] Seoul Natl Univ, Lab Dev Biol & Genom, Res Inst Vet Sci, Coll Vet Med,Korea Mouse Phenotyping Ctr, Seoul, South Korea

[11] Ewha Womans Univ, Natl Creat Initiat, Immune & Vasc Cell Network Res Ctr, Dept Life Sci, Seoul, South Korea

[12] ITMO Univ, Comp Technol Dept, St Petersburg, Russia

来源：

CIRCULATION RESEARCH | 2018年 / 123卷 / 10期

基金：

新加坡国家研究基金会; 美国国家卫生研究院; 加拿大健康研究院;

关键词：

atherosclerosis; flow cytometry; foam cells; macrophages; mice; RNA-seq; SMOOTH-MUSCLE-CELLS; MONOCYTE-DERIVED CELLS; DENDRITIC CELLS; CHOLESTEROL; ACCUMULATION; ARTERIAL; PROLIFERATION; ATHEROGENESIS; PATHOGENESIS; RECRUITMENT;

D O I：

10.1161/CIRCRESAHA.118.312804

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Rationale: Monocyte infiltration into the subintimal space and its intracellular lipid accumulation are the most prominent features of atherosclerosis. To understand the pathophysiology of atherosclerotic disease, we need to understand the characteristics of lipid-laden foamy macrophages in the subintimal space during atherosclerosis. Objective: We sought to examine the transcriptomic profiles of foamy and nonfoamy macrophages isolated from atherosclerotic intima. Methods and Results: Single-cell RNA sequencing analysis of CD45(+) leukocytes from murine atherosclerotic aorta revealed that there are macrophage subpopulations with distinct differentially expressed genes involved in various functional pathways. To specifically characterize the intimal foamy macrophages of plaque, we developed a lipid staining-based flow cytometric method for analyzing the lipid-laden foam cells of atherosclerotic aortas. We used the fluorescent lipid probe BODIPY493/503 and assessed side-scattered light as an indication of cellular granularity. (BODIPYSSChi)-S-hi foamy macrophages were found residing in intima and expressing CD11c. Foamy macrophage accumulation determined by flow cytometry was positively correlated with the severity of atherosclerosis. Bulk RNA sequencing analysis showed that compared with nonfoamy macrophages, foamy macrophages expressed few inflammatory genes but many lipid-processing genes. Intimal nonfoamy macrophages formed the major population expressing IL (interleukin)-1 beta and many other inflammatory transcripts in atherosclerotic aorta. Conclusions: RNA sequencing analysis of intimal macrophages from atherosclerotic aorta revealed that lipid-loaded plaque macrophages are not likely the plaque macrophages that drive lesional inflammation.

引用

页码：1127 / 1142

页数：16

共 52 条

[21] Optimization and validation of an 8-color intracellular cytokine staining (ICS) assay to quantify antigen-specific T cells induced by vaccination [J].