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

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. BODIPYhiSSChi 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)-1β 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.

journal_name

Circ Res

journal_title

Circulation research

authors

Kim K,Shim D,Lee JS,Zaitsev K,Williams JW,Kim KW,Jang MY,Seok Jang H,Yun TJ,Lee SH,Yoon WK,Prat A,Seidah NG,Choi J,Lee SP,Yoon SH,Nam JW,Seong JK,Oh GT,Randolph GJ,Artyomov MN,Cheong C,Choi JH

doi

10.1161/CIRCRESAHA.118.312804

subject

Has Abstract

pub_date

2018-10-26 00:00:00

pages

1127-1142

issue

10

eissn

0009-7330

issn

1524-4571

journal_volume

123

pub_type

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