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PMID: 17200719 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

The Journal of clinical investigation ·Vol. 117 ·No. 1 ·2007-01-00 ·Pages 195-205

Swirski FK, Libby P, Aikawa E, Alcaide P, Luscinskas FW, Weissleder R, Pittet MJ

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-6C(hi) monocyte subset increased dramatically in hypercholesterolemic apoE-deficient mice consuming a high-fat diet, with the number of Ly-6C(hi) cells doubling in the blood every month. Ly-6C(hi) 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-6C(hi) to Ly-6C(lo) conversion and subsided upon statin-induced cholesterol reduction. Conversely, the number of Ly-6C(lo) cells remained unaffected. Thus, we believe that Ly-6C(hi) monocytes represent a newly recognized component of the inflammatory response in experimental atherosclerosis.

MeSH Terms
Animals Antibodies, Monoclonal Antigens, Ly/immunology Apolipoproteins E/blood,deficiency,genetics Atherosclerosis/blood,genetics Disease Models, Animal Flow Cytometry Hypercholesterolemia/blood Macrophages/cytology,physiology Mice Mice, Inbred C57BL Mice, Knockout Monocytes/cytology,physiology
Chemicals
Antibodies, Monoclonal Antigens, Ly Apolipoproteins E Ly-6C antigen, mouse
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Swirski Filip K
Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA. [email protected]
Libby Peter
Aikawa Elena
Alcaide Pilar
Luscinskas F William
Weissleder Ralph
Pittet Mikael J
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI29950
Email
[email protected]
Published
2007-01-00
Pages
195-205
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC1716211
Subset
IM
Grants
NHLBI NIH HHS · HL36028 · United States
NHLBI NIH HHS · HL53393 · United States
NCI NIH HHS · R24 CA69246 · United States
NHLBI NIH HHS · U01 HL080731 · United States
NCI NIH HHS · P01 CA069246 · United States
NHLBI NIH HHS · P01 HL036028 · United States
PHS HHS · P01-A154904 · United States
NHLBI NIH HHS · R01 HL034636 · United States
NHLBI NIH HHS · R01HL034636 · United States
Corrections
CommentIn
PMID: 17200712
External Links
PubMed source DOI: 10.1172/JCI29950 PMC Full Text View journal details
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