期刊
CIRCULATION RESEARCH
卷 123, 期 10, 页码 1127-1142出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCRESAHA.118.312804
关键词
atherosclerosis; flow cytometry; foam cells; macrophages; mice; RNA-seq
资金
- Bio and Medical Technology Development Program of the National Research Foundation
- Korean government (Ministry of Health and Welfare, Ministry of Science and ICT) [2016M3A9D5A01952413, 2018R1A2B6003393, 2015M3A9B6029138]
- Korean Health Technology RD Project [HI15C0399]
- Ministry of Health, Welfare, and Family Affairs
- Canadian Institutes of Health Research (CIHR) [FRN 125933]
- Canadian Institutes of Health Research (CIHR Foundation ) [148363]
- Canadian Institutes of Health Research (Canada Research Chair) [950-231335]
- American Heart Association [17POST33410473]
- Government of Russian Federation grant [074-U01]
- National Cancer Institute Cancer Center Support [P30 CA91842]
- ICTS/CTSA grant from the National Center for Research Resources (NCRR)-a component of the National Institutes of Health (NIH) [UL1TR002345]
- ICTS/CTSA grant from the National Center for Research Resources (NCRR)-NIH Roadmap for Medical Research
- National Research Foundation of Korea [2015M3A9B6029138, 2016M3A9D5A01952413, 2018R1A2B6003393, 22A20130012056] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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.
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