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

Title
Transcriptome Analysis Reveals Nonfoamy Rather Than Foamy Plaque Macrophages Are Proinflammatory in Atherosclerotic Murine Models
Author
남진우
Keywords
atherosclerosis; flow cytometry; foam cells; macrophages; mice; RNA-seq
Issue Date
2018-08
Publisher
LIPPINCOTT WILLIAMS & WILKINS
Citation
CIRCULATION RESEARCH, v. 123, no. 10, page. 1127-1142
Abstract
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.
URI
https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.118.312804https://repository.hanyang.ac.kr/handle/20.500.11754/119607
ISSN
0009-7330; 1524-4571
DOI
10.1161/CIRCRESAHA.118.312804
Appears in Collections:
COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
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