title: Collagen-targeting vascular endothelial growth factor improves cardiac performance after myocardial infarction.
abstract: BACKGROUND
  Vascular endothelial growth factor (VEGF) is an important active protein for the induction of angiogenesis and improvement in cardiac function after myocardial ischemia; however, the lack of a delivery system targeted to the injured myocardium reduces the local therapeutic efficacy of VEGF and increases its possible adverse effects.
  
  
  RESULTS
  We produced a fusion protein (CBD-VEGF) consisting of VEGF and a collagen-binding domain (CBD). The fusion protein specifically bound to type I collagen in vitro. In addition, CBD-VEGF promoted human umbilical vein endothelial cell proliferation after binding to collagen, which indicates that it retained both growth factor activity and collagen-binding ability. When implanted subcutaneously in rats, collagen membranes loaded with CBD-VEGF were significantly vascularized. After it was injected into rats with acute myocardial infarction, CBD-VEGF was largely retained in the cardiac extracellular matrix, in which collagen I was rich. Four weeks after VEGF or CBD-VEGF was injected into the infarct border zone, cardiac function detected by echocardiography and hemodynamics was preserved in the CBD-VEGF group. Administration of CBD-VEGF also induced reduction of scar size, whereas native VEGF did not have these effects. In addition, a significant increase in the number of capillary vessels in infarcted hearts was found in the CBD-VEGF group.
  
  
  CONCLUSIONS
  The injection of CBD-VEGF improved cardiac function in rats with induced acute myocardial infarction. This could potentially provide a new treatment option for myocardial infarction.
authors.affiliation: Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Liang
authors.initials: L
authors.lastname: Ding
authors.forename: Yannan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Wenjie
authors.initials: W
authors.lastname: Sun
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
authors.forename: Hang
authors.initials: H
authors.lastname: Lin
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.forename: Lujie
authors.initials: L
authors.lastname: Zhang
authors.forename: Biao
authors.initials: B
authors.lastname: Xu
authors.forename: Jianwu
authors.initials: J
authors.lastname: Dai
mesh_terms: D000818:Animals; D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism*; D016503:Drug Delivery Systems; D004452:Echocardiography; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D017434:Protein Structure, Tertiary; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000493:pharmacokinetics*; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry / Q000235:genetics / Q000493:pharmacokinetics*
chemical_list: D024042:Collagen Type I; D011993:Recombinant Fusion Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A