title: The presence of leukocyte CC-chemokine receptor 2 in CCR2 knockout mice promotes atherogenesis.
abstract: OBJECTIVE
  To selectively determine the role of leukocyte CC-chemokine receptor 2 (CCR2) in atherogenesis.
  
  
  RESULTS
  Bone marrow progenitor cells harvested from CCR2(+/+) mice were transplanted into irradiated CCR2(-/-) mice, representing the whole-body absence of CCR2 except in leukocytes. Transplantation of CCR2(-/-) bone marrow into CCR2(-/-) mice served as control. Eight weeks after bone marrow transplantation, the diet of regular chow was switched to a high-cholesterol diet for another 10 weeks in order to induce atherosclerosis. No significant differences in serum cholesterol and triglyceride levels were observed between the two groups. However, the mean cross-sectional aortic root lesion area of CCR2(+/+)-->CCR2(-/-) mice amounted up to 12.28+/-3.28x10(4) microm(2), compared with only 3.08+/-0.74 x 10(4) microm(2) observed in the CCR2(-/-)-->CCR2(-/-) group. Thus, the presence of CCR2 exclusively on leukocytes induces a fourfold increase in aortic lesion area. This extent of lesion development was comparable to C57Bl/6 mice receiving CCR2(+/+) bone marrow (10.08+/-3.30x10(4) microm(2)).
  
  
  CONCLUSIONS
  These results point at a dominant role of leukocyte CCR2 in atherogenesis, implying that CCR2 from nonleukocyte sources, like endothelial cells or smooth muscle cells, is less critical in the initiation of atherosclerosis. Pharmacological inhibition of leukocyte CCR2 function might be a promising strategy to prevent atherosclerosis.
authors.affiliation: Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research (LACDR), Gorlaeus Laboratories, Leiden University, The Netherlands.
authors.forename: Jian
authors.initials: J
authors.lastname: Guo
authors.forename: Miranda
authors.initials: M
authors.lastname: Van Eck
authors.forename: Vivian
authors.initials: V
authors.lastname: de Waard
authors.forename: Nobuyo
authors.initials: N
authors.lastname: Maeda
authors.forename: G Martin
authors.initials: GM
authors.lastname: Benson
authors.forename: Pieter H E
authors.initials: PH
authors.lastname: Groot
authors.forename: Theo J C
authors.initials: TJ
authors.lastname: Van Berkel
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology*; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D003094:Collagen / Q000378:metabolism; D017931:DNA Primers; D004036:Diet, Atherogenic; D018380:Hematopoietic Stem Cell Transplantation; D007962:Leukocytes / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000235:genetics* / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood
chemical_list: C515335:Ccr2 protein, mouse; D017931:DNA Primers; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D014280:Triglycerides; D003094:Collagen; D002784:Cholesterol