Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata.
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.
Swirski
Filip K
FK
Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA. mpittet@hms.harvard.edu
Libby
Peter
P
Aikawa
Elena
E
Alcaide
Pilar
P
Luscinskas
F William
FW
Weissleder
Ralph
R
Pittet
Mikael J
MJ
D000818:Animals; D000911:Antibodies, Monoclonal; D000950:Antigens, Ly / Q000276:immunology*; D001057:Apolipoproteins E / Q000097:blood / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000097:blood* / Q000235:genetics; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006937:Hypercholesterolemia / Q000097:blood*; D008264:Macrophages / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology / Q000502:physiology
D000911:Antibodies, Monoclonal; D000950:Antigens, Ly; D001057:Apolipoproteins E; C494192:Ly-6C antigen, mouse