title: Endothelial progenitor cells induce transplant arteriosclerosis via VEGFR-1/2 activity.
abstract: BACKGROUND
  Acute rejection (AR) after organ transplantation results in transplant arteriosclerosis (TA). Endothelial progenitor cells (EPCs) are involved in tissue repair and blood vessel formation but are suspected to be a cause of TA.
  
  
  METHODS
  In this study, we introduced a syngeneic and allogeneic abdominal aortic transplant model with C57BL/6 and BALB/c mice. Syngeneic and allogeneic grafts were histopathologically analyzed after transplantation. Bone marrow-derived EPCs were injected into transplant model animals to observe their distribution and temporal concentration changes. Changes of vascular endothelial growth factor receptor 1 (VEGFR-1), phosphorylated VEGFR-1 (pVEGFR-1), VEGFR-2, pVEGFR-2, protein kinase B (Akt), pAkt, extracellular signal-regulated kinase 1 (Erk1), pErk1 levels in EPCs upon VEGF165 and the VEGFR inhibitor Vandetanib exposure were analyzed in vitro with western blotting.
  
  
  RESULTS
  In the allogeneic transplant group, two weeks after transplantation, formations of new intima layers could be observed, and its proliferation gradually increased to four and six weeks post-transplantation (p < 0.05), accompanied by significant arterial stenoses. Exogenous EPCs mainly localized to the damaged sites of the transplant arteries. In vivo, Vandetanib caused a significant dose dependent decrease of transplant hyperplasia (p < 0.05) and inhibited VEGF related proliferation, migration and adhesion of EPCs.
  
  
  CONCLUSIONS
  Vandetanib treatment can reduce arteriosclerosis induced by abdominal aorta transplantation by blocking VEGFRs in EPCs.
authors.affiliation: Department of Cardiothoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, No 180 Fenglin Road, Shanghai 200032, China.
authors.forename: Zhaohua
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Biological Product and Biochemistry Drug Division, Shanghai Institute for Food and Drug Control, No. 1500 Zhangheng Road, Shanghai 201203, China.
authors.forename: Can
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Cardiothoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, No 180 Fenglin Road, Shanghai 200032, China.
authors.forename: Shouguo
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Cardiothoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, No 180 Fenglin Road, Shanghai 200032, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Hong
authors.affiliation: Department of Cardiothoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, No 180 Fenglin Road, Shanghai 200032, China.
authors.forename: Fangshun
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Cardiothoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, No 180 Fenglin Road, Shanghai 200032, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Xia
authors.affiliation: Department of Cardiothoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, No 180 Fenglin Road, Shanghai 200032, China. Electronic address: Wangcs052914@163.com.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Wang
mesh_terms: D000818:Animals; D001011:Aorta / Q000637:transplantation*; D001161:Arteriosclerosis / Q000503:physiopathology*; D001854:Bone Marrow Cells / Q000166:cytology; D042783:Endothelial Cells / Q000166:cytology*; D005434:Flow Cytometry; D006084:Graft Rejection; D006085:Graft Survival; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D010880:Piperidines / Q000737:chemistry*; D011799:Quinazolines / Q000737:chemistry*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology*; D014184:Transplantation, Homologous; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D010880:Piperidines; D011799:Quinazolines; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; C452423:vandetanib
keywords: Endothelial progenitor cells; Transplant arteriosclerosis; VEGFR-1/2