title: LOX-1 deletion and macrophage trafficking in atherosclerosis.
abstract: BACKGROUND
  Atherosclerosis is associated with macrophage accumulation. LOX-1 has been shown to induce macrophage attachment, and its deletion (LOX-1 knockout, KO) reduces atherosclerosis in LDLr KO mice fed a high cholesterol diet. We examined differences in macrophage trafficking in age-matched wild type, LOX-1 KO, LDLr KO, and LDLr/LOX-1 double KO mice.
  
  
  METHODS
  Sections of aortas of mice fed high cholesterol diet were collected at weeks 0, 4, 8, 12 and 19 and analyzed by immunohistochemistry and flow cytometry.
  
  
  RESULTS
  In the LDLr KO mice aorta, CD68 positivity (macrophage accumulation) increased over time up to 12 weeks, and then the accumulation fell modestly but significantly. The periaortal fat and adventitia showed more CD68 positivity than the media and intima. This pattern was also evident in the non-atherosclerotic areas. Importantly, LOX-1 KO and LDLr-LOX-1 double KO mice showed diminished CD68 positivity in comparison to wild type and LDLR KO mice, respectively. Further, macrophages from LOX-1 KO mice revealed a marked reduction in migration (vs. macrophages from wild type mice) in in vitro migration assay.
  
  
  CONCLUSIONS
  LOX-1 deletion translates into reduction in macrophage trafficking in the aorta of LDLr KO mice. Most of the macrophage trafficking appears in the subadventitial regions.
authors.affiliation: Division of Cardiovascular Medicine, University of Arkansas for Medical Sciences and the Central Arkansas Veterans Healthcare System, Little Rock, AR, USA. Electronic address: ZDing@uams.edu.
authors.forename: Zufeng
authors.initials: Z
authors.lastname: Ding
authors.forename: Adam Milton
authors.initials: AM
authors.lastname: Mizeracki
authors.forename: Changping
authors.initials: C
authors.lastname: Hu
authors.forename: Jawahar L
authors.initials: JL
authors.lastname: Mehta
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D001011:Aorta / Q000378:metabolism; D050197:Atherosclerosis / Q000503:physiopathology*; D002465:Cell Movement / Q000502:physiology; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000172:deficiency; D051127:Scavenger Receptors, Class E / Q000172:deficiency*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D011973:Receptors, LDL; D051127:Scavenger Receptors, Class E; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C495138:Olr1 protein, mouse
keywords: Atherosclerosis; LOX-1; Macrophages