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Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata
Filip K. Swirski, … , Ralph Weissleder, Mikael J. Pittet
Filip K. Swirski, … , Ralph Weissleder, Mikael J. Pittet
Published January 2, 2007
Citation Information: J Clin Invest. 2007;117(1):195-205. https://doi.org/10.1172/JCI29950.
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Research Article Article has an altmetric score of 23

Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata

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Abstract

Macrophage accumulation participates decisively in the development and exacerbation of atherosclerosis. Circulating monocytes, the precursors of macrophages, display heterogeneity in mice and humans, but their relative contribution to atherogenesis remains unknown. We report here that the Ly-6Chi monocyte subset increased dramatically in hypercholesterolemic apoE–deficient mice consuming a high-fat diet, with the number of Ly-6Chi cells doubling in the blood every month. Ly-6Chi monocytes adhered to activated endothelium, infiltrated lesions, and became lesional macrophages. Hypercholesterolemia-associated monocytosis (HAM) developed from increased survival, continued cell proliferation, and impaired Ly-6Chi to Ly-6Clo conversion and subsided upon statin-induced cholesterol reduction. Conversely, the number of Ly-6Clo cells remained unaffected. Thus, we believe that Ly-6Chi monocytes represent a newly recognized component of the inflammatory response in experimental atherosclerosis.

Authors

Filip K. Swirski, Peter Libby, Elena Aikawa, Pilar Alcaide, F. William Luscinskas, Ralph Weissleder, Mikael J. Pittet

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Figure 5

Ly-6Chi monocytes adhere preferentially to TNF-α–activated endothelium, accumulate in lesions, and differentiate to macrophages in vivo.

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Ly-6Chi monocytes adhere preferentially to TNF-α–activated endothelium, ...
(A) Purified Ly-6Chi monocyte phenotype after 24 hours in culture. (B) Adherence of blood monocytes on TNF-α–treated MHECs under laminar flow conditions. Monocyte subsets were isolated from the blood of apoE+/+ and apoE–/– mice on chow and Western diet. (C) Relative proportion of blood monocytes expected to adhere to activated endothelium, based on the capacity of each subset to adhere and their average abundance in peripheral blood of apoE–/– mice on Western diet for 25 weeks. (D) Ly-6C, F4/80, and I-Ab expression of CD45.2+ Ly-6Chi monocytes retrieved from aortas and spleens 24 hours after transfer into CD45.1+ mice (both donor and recipient apoE–/– mice consuming a Western diet). Monocytes cultured in vitro were also analyzed. (E) F4/80 and Ly-6C coexpression on CD45.2+ donor cells retrieved from aortas. (F) In vivo aortic accumulation of [111In]oxine-labeled Ly-6Chi and Ly-6Clo monocytes 24 hours after adoptive transfer in apoE–/– mice on Western diet. (G) Phosphorimager plates depicting relative distribution of signal in aortas of apoE–/– mice that received equal numbers of Ly-6Chi apoE–/– or Ly-6Clo apoE–/– monocytes. (H) Relative proportion of Ly-6Chi and Ly-6Clo monocytes expected to accumulate in atherosclerotic aortas, based on the capacity of each subset for aortic accumulation and their average abundance in peripheral blood of apoE–/– mice on Western diet for 25 weeks. Shown are 1 of 2–3 independent experiments. Student’s t test was used.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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