title: Impaired CXCR4 expression and cell engraftment of bone marrow-derived cells from aged atherogenic mice.
abstract: OBJECTIVE
  Reduced numbers and activity of circulating progenitor cells are associated with aging and have been linked with coronary artery disease. To determine the impact of aging and atherosclerotic disease on the chemotaxic activity of bone marrow derived cells (BMCs), we examined CXCR4 surface expression on BMCs from aged and atherosclerotic mice.
  
  
  METHODS
  CXCR4 expression and cellular mobility were compared between BMCs of young (6-week old) ApoE null mice (ApoE(-/-)) and aged ApoE(-/-) mice that had been fed with a high-fat, high-cholesterol diet for 6-months.
  
  
  RESULTS
  Age and atherosclerosis correlated with significantly lower surface expression of CXCR4 that was less inducible by calcium. The impaired calcium response was associated with defective calcium influx and was partially recovered by treatment with the calcium ionophore ionomycin. ApoE(-/-) mice fed high fat diet for 6-months had defective CXCR4 expression and SDF-1 regulation that is equivalent to that of 24-month old wild type mice. BMCs from aged, atherogenic ApoE(-/-) mice also displayed defective homing to SDF-1, and the animals had lower serum and bone marrow levels of SDF-1.
  
  
  CONCLUSIONS
  Evolution of atherosclerosis in ApoE(-/-) mice is paralleled by progressive loss of mobility of BMCs with reductions of CXCR4 expression, and reduced levels of SDF-1 in both serum and bone marrow. These changes mute the homing capability of BMCs and may contribute to the progression of atherosclerosis in this model.
authors.affiliation: Department of Cardiology, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Qiyuan
authors.initials: Q
authors.lastname: Xu
authors.forename: Jian'An
authors.initials: J
authors.lastname: Wang
authors.forename: Jinlin
authors.initials: J
authors.lastname: He
authors.forename: Mingsheng
authors.initials: M
authors.lastname: Zhou
authors.forename: Jennipher
authors.initials: J
authors.lastname: Adi
authors.forename: Keith A
authors.initials: KA
authors.lastname: Webster
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D017209:Apoptosis / Q000187:drug effects; D050197:Atherosclerosis / Q000209:etiology / Q000503:physiopathology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002465:Cell Movement; D002470:Cell Survival / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000096:biosynthesis; D059305:Diet, High-Fat; D051379:Mice; D018345:Mice, Knockout; D019718:Receptors, CXCR4 / Q000096:biosynthesis*
chemical_list: D001057:Apolipoproteins E; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D019718:Receptors, CXCR4; D002118:Calcium