Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice.
Recruitment of blood monocytes into the arterial subendothelium is one of the earliest steps in atherogenesis. Monocyte chemoattractant protein-1 (MCP-1), a CC chemokine, is one likely signal involved in this process. To test MCP-1's role in atherogenesis, low density lipoprotein (LDL) receptor-deficient mice were made genetically deficient for MCP-1 and fed a high cholesterol diet. Despite having the same amount of total and fractionated serum cholesterol as LDL receptor-deficient mice with wild-type MCP-1 alleles, LDL receptor/MCP-1-deficient mice had 83% less lipid deposition throughout their aortas. Consistent with MCP-1 's monocyte chemoattractant properties, compound-deficient mice also had fewer macrophages in their aortic walls. Thus, MCP-1 plays a unique and crucial role in the initiation of atherosclerosis and may provide a new therapeutic target in this disorder.
Gu
L
L
Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Okada
Y
Y
Clinton
S K
SK
Gerard
C
C
Sukhova
G K
GK
Libby
P
P
Rollins
B J
BJ
D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001161:Arteriosclerosis / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D001483:Base Sequence; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D004036:Diet, Atherogenic; D005260:Female; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008264:Macrophages / Q000473:pathology / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000502:physiology; D016133:Polymerase Chain Reaction; D011973:Receptors, LDL / Q000172:deficiency*
D018932:Chemokine CCL2; D017931:DNA Primers; D008055:Lipids; D011973:Receptors, LDL