title: VEGF gene therapy cooperatively recruits molecules from the immune system and stimulates cell homing and angiogenesis in refractory angina.
abstract: New vessels are formed in response to stimuli from angiogenic factors, a process in which paracrine signaling is fundamental.
  
  
  
  To investigate the cooperative paracrine signaling profile in response to Vascular Endothelial Growth Factor (VEGF) gene therapy in patients with coronary artery disease (CAD) and refractory angina.
  
  
  
  A cohort study was conducted in which plasma was collected from patients who underwent gene therapy with a plasmid expressing VEGF 165 (10) and from surgical procedure controls (4). Blood samples were collected from both groups prior to baseline and on days 3, 9 and 27 after the interventions and subjected to systemic analysis of protein expression (Interleukin-6, IL-6; Tumor Necrosis Factor-α, TNF-α; Interleukin-10, IL-10; Stromal Derived Factor-1 α, SDF-1α; VEGF; Angiopoietin-1, ANGPT-1; and Endothelin-1, ET-1) using the enzyme-linked immunosorbent assay (ELISA).
  
  
  
  Analysis showed an increase in proinflammatory IL-6 (p=0.02) and ET-1 (p=0.05) on day 3 after gene therapy and in VEGF (p=0.02) on day 9. A strong positive correlation was found between mobilization of endothelial progenitor cells and TNF-α on day 9 (r=0.71; p=0.03). Furthermore, a strong correlation between β-blockers, antiplatelets, and vasodilators with SDF-1α baseline in the group undergoing gene therapy was verified (r=0.74; p=0.004).
  
  
  
  Analysis of cooperative paracrine signaling after VEGF gene therapy suggests that the immune system cell and angiogenic molecule expression as well as the endothelial progenitor cell mobilization are time-dependent, influenced by chronic inflammatory process and continuous pharmacological treatment.
authors.affiliation: Laboratório de Cardiologia Molecular e Celular (Serviço de Medicina Experimental)/Secretaria de Cirurgia, Instituto de Cardiologia/Fundação Universitária de Cardiologia (IC/FUC), Brazil.
authors.forename: Bruna
authors.initials: B
authors.lastname: Eibel
authors.affiliation: Laboratório de Cardiologia Molecular e Celular (Serviço de Medicina Experimental)/Secretaria de Cirurgia, Instituto de Cardiologia/Fundação Universitária de Cardiologia (IC/FUC), Brazil.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Markoski
authors.affiliation: Laboratório de Cardiologia Molecular e Celular (Serviço de Medicina Experimental)/Secretaria de Cirurgia, Instituto de Cardiologia/Fundação Universitária de Cardiologia (IC/FUC), Brazil.
authors.forename: Clarissa G
authors.initials: CG
authors.lastname: Rodrigues
authors.affiliation: Faculdade de Desenvolvimento do Rio Grande do Sul (FADERGS), Brazil.
authors.forename: Thiago
authors.initials: T
authors.lastname: Dipp
authors.affiliation: Instituto do Coração/Faculdade de Medicina da Universidade de São Paulo (INCOR/FMUSP), Brazil.
authors.forename: Felipe B
authors.initials: FB
authors.lastname: de Salles
authors.affiliation: Laboratório de Cardiologia Molecular e Celular (Serviço de Medicina Experimental)/Secretaria de Cirurgia, Instituto de Cardiologia/Fundação Universitária de Cardiologia (IC/FUC), Brazil.
authors.forename: Imarilde I
authors.initials: II
authors.lastname: Giusti
authors.affiliation: Universidade Luterana do Brasil (ULBRA), Brazil.
authors.forename: Nance B
authors.initials: NB
authors.lastname: Nardi
authors.affiliation: Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil.
authors.forename: Rodrigo D M
authors.initials: RD
authors.lastname: Plentz
authors.affiliation: Laboratório de Cardiologia Molecular e Celular (Serviço de Medicina Experimental)/Secretaria de Cirurgia, Instituto de Cardiologia/Fundação Universitária de Cardiologia (IC/FUC), Brazil; Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil. Electronic address: kalil.renato@gmail.com.
authors.forename: Renato A K
authors.initials: RA
authors.lastname: Kalil
mesh_terms: D000368:Aged; D000787:Angina Pectoris / Q000235:genetics / Q000276:immunology / Q000628:therapy; D003324:Coronary Artery Disease / Q000235:genetics / Q000276:immunology / Q000628:therapy; D066026:Endothelial Progenitor Cells / Q000276:immunology*; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000276:immunology; D019899:Paracrine Communication / Q000235:genetics / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000276:immunology
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
keywords: Angiogenesis; Cell homing; Coronary artery disease; Gene therapy; Refractory angina; Vascular endothelial growth factor