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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
- Authors
- Kim, Kyeongdae; Shim, Dahee; Lee, Jun Seong; Zaitsev, Konstantin; Williams, Jesse W.; Kim, Ki-Wook; Jang, Man-Young; Jang, Hyung Seok; Yun, Tae Jin; Lee, Seung Hyun; Yoon, Won Kee; Prat, Annik; Seidah, Nabil G.; Choi, Jungsoon; Lee, Seung-Pyo; Yoon, Sang-Ho; Nam, Jin Wu; Seong, Je Kyung; Oh, Goo Taeg; Randolph, Gwendalyn J.; Artyomov, Maxim N.; Cheong, Cheolho; Choi, Jae-Hoon
- Ewha Authors
- 오구택
- SCOPUS Author ID
- 오구택
- Issue Date
- 2018
- Journal Title
- CIRCULATION RESEARCH
- ISSN
- 0009-7330
1524-4571
- Citation
- CIRCULATION RESEARCH vol. 123, no. 10, pp. 1127 - 1142
- Keywords
- atherosclerosis; flow cytometry; foam cells; macrophages; mice; RNA-seq
- Publisher
- LIPPINCOTT WILLIAMS &
WILKINS
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- 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.
- DOI
- 10.1161/CIRCRESAHA.118.312804
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
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