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AdVEGF-B186 and AdVEGF-DΔNΔC induce angiogenesis and increase perfusion in porcine myocardium
  1. Jussi Nurro1,
  2. Paavo J Halonen1,
  3. Antti Kuivanen1,
  4. Miikka Tarkia2,3,
  5. Antti Saraste2,
  6. Krista Honkonen1,
  7. Johanna Lähteenvuo1,
  8. Tuomas T Rissanen1,4,
  9. Juhani Knuuti2,
  10. Seppo Ylä-Herttuala1,5,6
  1. 1Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland
  2. 2Turku PET Centre, Turku University Hospital, Turku, Finland
  3. 3Department of Pharmacology, University of Helsinki, Helsinki, Finland
  4. 4Department of Internal Medicine, Central Hospital of North Karelia, Joensuu, Finland
  5. 5Science Service Center, Kuopio University Hospital, Kuopio, Finland
  6. 6Gene Therapy Unit, Kuopio University Hospital, Kuopio, Finland
  1. Correspondence to Professor Seppo Ylä-Herttuala, Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute, University of Eastern Finland, P.O. Box 1627, Kuopio FIN-70211, Finland; seppo.ylaherttuala{at}uef.fi

Abstract

Objective 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-B186 and 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.

Methods Intramyocardial adenoviral (Ad) VEGF-B186 or AdVEGF-DΔNΔC gene transfers were given endovascularly into the porcine posterolateral wall of the left ventricle (n=34). Six days later, PET 15O-imaging for myocardial perfusion and coronary angiography were performed.

Results AdVEGF-B186 and AdVEGF-DΔNΔC induced 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-B186 and 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.

Conclusions Both AdVEGF-B186 and AdVEGF-DΔNΔC gene 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.

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