title: AdVEGF-B186 and AdVEGF-DΔNΔC induce angiogenesis and increase perfusion in porcine myocardium.
abstract: Coronary heart disease remains a significant clinical problem, and new therapies are needed especially for patients with refractory angina for whom the current therapies do not provide sufficient relief. The aim of this study was to find out if angiogenic gene therapy using new members of the vascular endothelial growth factor (VEGF) family, VEGF-B186and VEGF-DΔNΔC, increase myocardial perfusion as measured by the positron emission tomography (PET)15O-imaging, and whether there would be coronary steal effect to the contralateral side. Furthermore, safety of intramyocardial angiogenic adenoviral gene transfer was evaluated.
  
  
  
  Intramyocardial adenoviral (Ad) VEGF-B186or AdVEGF-DΔNΔCgene transfers were given endovascularly into the porcine posterolateral wall of the left ventricle (n=34). Six days later, PET15O-imaging for myocardial perfusion and coronary angiography were performed.
  
  
  
  AdVEGF-B186and AdVEGF-DΔNΔCinduced angiogenesis and increased total microvascular area 1.8-fold (95% CI 0.2 to 3.5) and 2.8-fold (95% CI 1.4 to 4.3), respectively. At rest, perfusion was maintained at normal levels, but at stress, relative perfusion was increased 1.4-fold (95% CI 1.1 to 1.7) for AdVEGF-B186and 1.3-fold (95% CI 1.0 to 1.7) for AdVEGF-DΔNΔC, without causing coronary steal effect in the control area. The therapy was well tolerated and did not lead to any significant changes in laboratory safety parameters.
  
  
  
  Both AdVEGF-B186and AdVEGF-DΔNΔCgene transfers induced efficient angiogenesis in the myocardium resulting in an increased myocardial perfusion measured by PET. Importantly, local perfusion increase did not induce any coronary steal effect. As such, both treatments seem suitable new candidates for the induction of therapeutic angiogenesis for the treatment of refractory angina.
authors.affiliation: Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland.
authors.forename: Jussi
authors.initials: J
authors.lastname: Nurro
authors.affiliation: Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland.
authors.forename: Paavo J
authors.initials: PJ
authors.lastname: Halonen
authors.affiliation: Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Kuivanen
authors.affiliation: Turku PET Centre, Turku University Hospital, Turku, Finland Department of Pharmacology, University of Helsinki, Helsinki, Finland.
authors.forename: Miikka
authors.initials: M
authors.lastname: Tarkia
authors.affiliation: Turku PET Centre, Turku University Hospital, Turku, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Saraste
authors.affiliation: Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland.
authors.forename: Krista
authors.initials: K
authors.lastname: Honkonen
authors.affiliation: Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Lähteenvuo
authors.affiliation: Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland Department of Internal Medicine, Central Hospital of North Karelia, Joensuu, Finland.
authors.forename: Tuomas T
authors.initials: TT
authors.lastname: Rissanen
authors.affiliation: Turku PET Centre, Turku University Hospital, Turku, Finland.
authors.forename: Juhani
authors.initials: J
authors.lastname: Knuuti
authors.affiliation: Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland Science Service Center, Kuopio University Hospital, Kuopio, Finland Gene Therapy Unit, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Seppo
authors.initials: S
authors.lastname: Ylä-Herttuala
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017023:Coronary Angiography; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000378:metabolism*; D004452:Echocardiography; D005260:Female; D018014:Gene Transfer Techniques / Q000009:adverse effects; D005822:Genetic Vectors; D023421:Models, Animal; D055414:Myocardial Perfusion Imaging / Q000379:methods; D009206:Myocardium / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D049268:Positron-Emission Tomography; D015398:Signal Transduction; D034421:Sus scrofa; D013997:Time Factors; D015854:Up-Regulation; D042561:Vascular Endothelial Growth Factor B / Q000096:biosynthesis* / Q000235:genetics; D042643:Vascular Endothelial Growth Factor D / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D042561:Vascular Endothelial Growth Factor B; D042643:Vascular Endothelial Growth Factor D