title: Ultrasound molecular imaging of angiogenesis induced by mutant forms of hypoxia-inducible factor-1α.
abstract: OBJECTIVE
  Targeted point mutants of hypoxia-inducible factor-1α (HIF-1α) are potential optimal agents for angiogenesis therapy. Data are limited regarding the angiogenic response of HIF-1α mutants. We aimed to compare the angiogenic effect of wild-type and mutant HIF-1α by contrast ultrasound molecular imaging (UMI) of α(v)-integrin expression.
  
  
  RESULTS
  The wild-type gene of human HIF-1α, a gene with double mutations (HIF-1α(564/803)), a gene with triple mutations (HIF-1α(564/803/402)), or the LacZ gene (control) was transfected into the ischaemic hind limbs of C57BL/6 mice using an adenovirus vector. The video intensity of microbubbles targeted to α(v)-integrins in the ischaemic limbs increased along with the number of point mutations of HIF-1α. Immunohistochemical expression of endothelial α(v)-integrins was higher in the mutant HIF-1α(564/803/402) group than the other groups as was the density of both capillaries and arterioles in ischaemic muscle. Expression of both the mRNA and protein for HIF-1α and VEGF was significantly higher in the mutant HIF-1α(564/803/402) group than in the other groups. The half-life of HIF-1α and VEGF mRNA was longer in HIF-1α mutant-transfected cells than in wild-type HIF-1α or LacZ-transfected cells.
  
  
  CONCLUSIONS
  HIF-1α mutants were more effective for enhancing angiogenesis in ischaemic muscle tissue than wild-type HIF-1α, and the response could be qualitatively evaluated by UMI of α(v)-integrins expression.
authors.affiliation: Department of Cardiology and Key Laboratory of Organ Failure, Ministry of Education,  Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515,  China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Xie
authors.forename: Yulin
authors.initials: Y
authors.lastname: Liao
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Juefei
authors.initials: J
authors.lastname: Wu
authors.forename: Cheng
authors.initials: C
authors.lastname: Liu
authors.forename: Wanling
authors.initials: W
authors.lastname: Xuan
authors.forename: Mingyan
authors.initials: M
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Yili
authors.initials: Y
authors.lastname: Liu
authors.forename: Pingsheng
authors.initials: P
authors.lastname: Wu
authors.forename: Jianping
authors.initials: J
authors.lastname: Bin
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002196:Capillaries / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000503:physiopathology; D002478:Cells, Cultured; D003287:Contrast Media; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D006207:Half-Life; D006614:Hindlimb; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis / Q000235:genetics*; D007150:Immunohistochemistry; D039564:Integrin alphaV / Q000378:metabolism*; D007511:Ischemia / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D045423:Microbubbles; D057054:Molecular Imaging / Q000379:methods*; D018482:Muscle, Skeletal / Q000098:blood supply*; D018919:Neovascularization, Physiologic; D017354:Point Mutation; D012333:RNA, Messenger / Q000378:metabolism; D012039:Regional Blood Flow; D013997:Time Factors; D014162:Transfection; D014463:Ultrasonography; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D003287:Contrast Media; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D039564:Integrin alphaV; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse