PMID- 10079097
OWN - NLM
STAT- MEDLINE
DCOM- 19990402
LR  - 20220309
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 103
IP  - 6
DP  - 1999 Mar
TI  - MCP-1 deficiency reduces susceptibility to atherosclerosis in mice that 
      overexpress human apolipoprotein B.
PG  - 773-8
AB  - The earliest recognizable atherosclerotic lesions are fatty streaks composed of 
      lipid-laden macrophages (foam cells). Circulating monocytes are the precursors of 
      these foam cells, but the molecular mechanisms that govern macrophage trafficking 
      through the vessel wall are poorly understood. Monocyte chemoattractant protein-1 
      (MCP-1), a member of the chemokine (chemotactic cytokine) family, is a potent 
      monocyte agonist that is upregulated by oxidized lipids. Recent studies in 
      hypercholesterolemic mice lacking apo E or the low-density lipoprotein receptor 
      have suggested a role for MCP-1 in monocyte recruitment to early atherosclerotic 
      lesions. To determine if MCP-1 is critically involved in atherogenesis in the 
      setting of elevated physiological plasma cholesterol levels, we deleted the MCP-1 
      gene in transgenic mice expressing human apo B. Here we report that the absence 
      of MCP-1 provides dramatic protection from macrophage recruitment and 
      atherosclerotic lesion formation in apo B transgenic mice, without altering 
      lipoprotein metabolism. Taken together with the results of earlier studies, these 
      data provide compelling evidence that MCP-1 plays a critical role in the 
      initiation of atherosclerosis.
FAU - Gosling, J
AU  - Gosling J
AD  - Gladstone Institute of Cardiovascular Disease, San Francisco, California 94141, 
      USA.
FAU - Slaymaker, S
AU  - Slaymaker S
FAU - Gu, L
AU  - Gu L
FAU - Tseng, S
AU  - Tseng S
FAU - Zlot, C H
AU  - Zlot CH
FAU - Young, S G
AU  - Young SG
FAU - Rollins, B J
AU  - Rollins BJ
FAU - Charo, I F
AU  - Charo IF
LA  - eng
GR  - P01 HL041633/HL/NHLBI NIH HHS/United States
GR  - R01 HL052773/HL/NHLBI NIH HHS/United States
GR  - HL-41633/HL/NHLBI NIH HHS/United States
GR  - HL-52773/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Apolipoproteins B)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cholesterol, HDL)
RN  - 0 (Lipoproteins)
RN  - 0 (Triglycerides)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - Animals
MH  - Aorta/pathology
MH  - Apolipoproteins B/*biosynthesis/genetics
MH  - Arteriosclerosis/*etiology/pathology
MH  - Chemokine CCL2/*deficiency/genetics
MH  - Cholesterol/blood
MH  - Cholesterol, HDL/blood
MH  - Foam Cells/cytology/*metabolism
MH  - Humans
MH  - Lipoproteins/*biosynthesis/genetics
MH  - Mice
MH  - Mice, Transgenic
MH  - Triglycerides/blood
PMC - PMC408147
EDAT- 1999/03/17 00:00
MHDA- 1999/03/17 00:01
PMCR- 1999/03/15
CRDT- 1999/03/17 00:00
PHST- 1999/03/17 00:00 [pubmed]
PHST- 1999/03/17 00:01 [medline]
PHST- 1999/03/17 00:00 [entrez]
PHST- 1999/03/15 00:00 [pmc-release]
AID - 05624 [pii]
AID - 10.1172/JCI5624 [doi]
PST - ppublish
SO  - J Clin Invest. 1999 Mar;103(6):773-8. doi: 10.1172/JCI5624.