title: VEGF 165 gene therapy for patients with refractory angina: mobilization of endothelial progenitor cells.
abstract: BACKGROUND
  Vascular endothelial growth factor (VEGF) induces mobilization of endothelial progenitor cells (EPCs) with the capacity for proliferation and differentiation into mature endothelial cells, thus contributing to the angiogenic process.
  
  
  OBJECTIVE
  We sought to assess the behavior of EPCs in patients with ischemic heart disease and refractory angina who received an intramyocardial injections of 2000 µg of VEGF 165 as the sole therapy.
  
  
  METHODS
  The study was a subanalysis of a clinical trial. Patients with advanced ischemic heart disease and refractory angina were assessed for eligibility. Inclusion criteria were as follows: signs and symptoms of angina and/or heart failure despite maximum medical treatment and a myocardial ischemic area of at least 5% as assessed by single-photon emission computed tomography (SPECT). Exclusion criteria were as follows: age > 65 years, left ventricular ejection fraction < 25%, and a diagnosis of cancer. Patients whose EPC levels were assessed were included. The intervention was 2000 µg of VEGF 165 plasmid injected into the ischemic myocardium. The frequency of CD34+/KDR+ cells was analyzed by flow cytometry before and 3, 9, and 27 days after the intervention.
  
  
  RESULTS
  A total of 9 patients were included, 8 males, mean age 59.4 years, mean left ventricular ejection fraction of 59.3% and predominant class III angina. The number of EPCs on day 3 was significantly higher than that at baseline (p = 0.03); however, that on days 9 and 27 was comparable to that at baseline.
  
  
  CONCLUSIONS
  We identified a transient mobilization of EPCs, which peaked on the 3th day after VEGF 165 gene therapy in patients with refractory angina and returned to near baseline levels on days 9 and 27.
authors.forename: Clarissa G
authors.initials: CG
authors.lastname: Rodrigues
authors.forename: Rodrigo D M
authors.initials: RD
authors.lastname: Plentz
authors.forename: Thiago
authors.initials: T
authors.lastname: Dipp
authors.forename: Felipe B
authors.initials: FB
authors.lastname: Salles
authors.forename: Imarilde I
authors.initials: II
authors.lastname: Giusti
authors.forename: Roberto T
authors.initials: RT
authors.lastname: Sant'Anna
authors.forename: Bruna
authors.initials: B
authors.lastname: Eibel
authors.forename: Ivo A
authors.initials: IA
authors.lastname: Nesralla
authors.forename: Melissa
authors.initials: M
authors.lastname: Markoski
authors.forename: Nance N
authors.initials: NN
authors.lastname: Beyer
authors.forename: Renato A K
authors.initials: RA
authors.lastname: Kalil
mesh_terms: D000787:Angina Pectoris / Q000628:therapy*; D002465:Cell Movement / Q000235:genetics* / Q000502:physiology; D042783:Endothelial Cells / Q000502:physiology*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D039902:Multipotent Stem Cells / Q000166:cytology / Q000502:physiology*; D017202:Myocardial Ischemia / Q000628:therapy; D018919:Neovascularization, Physiologic / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D013997:Time Factors; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D042461:Vascular Endothelial Growth Factor A