title: PlGF repairs myocardial ischemia through mechanisms of angiogenesis, cardioprotection and recruitment of myo-angiogenic competent marrow progenitors.
abstract: BACKGROUND
  Despite preclinical success in regenerating and revascularizing the infarcted heart using angiogenic growth factors or bone marrow (BM) cells, recent clinical trials have revealed less benefit from these therapies than expected.
  
  
  OBJECTIVE
  We explored the therapeutic potential of myocardial gene therapy of placental growth factor (PlGF), a VEGF-related angiogenic growth factor, with progenitor-mobilizing activity.
  
  
  RESULTS
  Myocardial PlGF gene therapy improves cardiac performance after myocardial infarction, by inducing cardiac repair and reparative myoangiogenesis, via upregulation of paracrine anti-apoptotic and angiogenic factors. In addition, PlGF therapy stimulated Sca-1(+)/Lin(-) (SL) BM progenitor proliferation, enhanced their mobilization into peripheral blood, and promoted their recruitment into the peri-infarct borders. Moreover, PlGF enhanced endothelial progenitor colony formation of BM-derived SL cells, and induced a phenotypic switch of BM-SL cells, recruited in the infarct, to the endothelial, smooth muscle and cardiomyocyte lineage.
  
  
  CONCLUSIONS
  Such pleiotropic effects of PlGF on cardiac repair and regeneration offer novel opportunities in the treatment of ischemic heart disease.
authors.affiliation: Stem Cell Translational Research, Institute of Biomedical Research and Innovation/RIKEN Center for Developmental Biology, Kobe, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Iwasaki
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Kawamoto
authors.forename: Marc
authors.initials: M
authors.lastname: Tjwa
authors.forename: Miki
authors.initials: M
authors.lastname: Horii
authors.forename: Saeko
authors.initials: S
authors.lastname: Hayashi
authors.forename: Akira
authors.initials: A
authors.lastname: Oyamada
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Shigefumi
authors.initials: S
authors.lastname: Suehiro
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
authors.forename: Takayuki
authors.initials: T
authors.lastname: Asahara
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D049109:Cell Proliferation; D004562:Electrocardiography / Q000379:methods; D005260:Female; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000737:chemistry; D006439:Hemodynamics; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000628:therapy; D009206:Myocardium / Q000473:pathology; D009389:Neovascularization, Pathologic; D010641:Phenotype; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration; D013234:Stem Cells / Q000166:cytology*
chemical_list: C000608036:PGF protein, human; C000608037:Pgf protein, mouse; C000608038:Pgf protein, rat; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D049452:Green Fluorescent Proteins