title: Overexpression of CXCL16 promotes a vulnerable plaque phenotype in Apolipoprotein E-Knockout Mice.
abstract: BACKGROUND
  CXCL16 has been shown to be involved in atherosclerotic lesion development, but its role in preexisting lesions is still unclear. This study aims to assess the effect of CXCL16 on the stability of preexisting lesions.
  
  
  METHODS
  We firstly measured plasma CXCL16 level in Apolipoprotein E-Knockout (ApoE KO) mice with either high-cholesterol diet (HCD) or normal diet (ND) by enzyme-linked immunosorbent assay (ELISA). Then, silastic collars were placed around the carotid arteries in HCD-ApoE KO mice to accelerate atherosclerotic lesions. Five weeks later, CXCL16 was overexpressed by intravenous injection of lentivirus carrying CXCL16 transgene. Two weeks after infection, lesions were stained with hematoxylin and eosin (HE) and with oil red O. Biomarkers in the lesions, such as MMPs, CCL2, VCAM-1 and TNF-α were measured by real-time polymerase chain reaction (RT-PCR), which indicate the instability of plaques.
  
  
  RESULTS
  The level of CXCL16 in plasma was higher in HCD-ApoE KO mice as compared to ND-ApoE KO mice. Circulating CXCL16 overexpression does not affect the size of preexisting plaques, but it leads to vulnerable plaque morphology and increases the expression of markers of plaque destabilization.
  
  
  CONCLUSIONS
  Systemic CXCL16 becomes much higher in atherosclerosis, and it could be a potential atherogenic biomarker. Overexpression of CXCL16 promotes the evolution of preexisting lesions to vulnerable plaques in ApoE KO mice.
authors.affiliation: Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Gui-wen
authors.initials: GW
authors.lastname: Yi
authors.forename: Qiu-tang
authors.initials: QT
authors.lastname: Zeng
authors.forename: Xiao-bo
authors.initials: XB
authors.lastname: Mao
authors.forename: Min
authors.initials: M
authors.lastname: Cheng
authors.forename: Xiao-fang
authors.initials: XF
authors.lastname: Yang
authors.forename: Hong-tao
authors.initials: HT
authors.lastname: Liu
authors.forename: Yi
authors.initials: Y
authors.lastname: Mao
authors.forename: Min
authors.initials: M
authors.lastname: Guo
authors.forename: Qin-wei
authors.initials: QW
authors.lastname: Ji
authors.forename: Yu-cheng
authors.initials: YC
authors.lastname: Zhong
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001915:Braces / Q000009:adverse effects; D002339:Carotid Arteries / Q000378:metabolism* / Q000473:pathology; D018932:Chemokine CCL2 / Q000235:genetics; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6 / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D002791:Cholesterol, Dietary / Q000008:administration & dosage / Q000009:adverse effects; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D058226:Plaque, Atherosclerotic / Q000097:blood* / Q000209:etiology / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; D002791:Cholesterol, Dietary; C498926:Cxcl16 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D020782:Matrix Metalloproteinases