Jens Kastrup

Department of Cardiology, The Heart Centre, University Hospital Rigshospitalet, Copenhagen,

Denmark

Abstract: Several vascular growth factors have the potential to induce angiogenesis in ischemic tissue. However, only vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) have been tested in clinical studies of patients with coronary artery disease. Several small and unblinded studies with either recombinant growth factor proteins or genes encoding the growth factors have been performed in patients with severe CAD and results have been encouraging, demonstrating both clinical improvement and evidence of angiogenesis. However, a few larger double-blind randomised placebo-controlled studies have not been able to confirm the initial high efficacy of the growth factor therapy. Ongoing clinical trials with increased gene dose will demonstrate whether the used methodologies and genes are effective. In future trials one have to consider whether improved transfection vectors, combination of genes and stem cells or gene transfected cells will enhance the efficacy of the treatments. The conducted clinical studies with growth factor therapies have all been without any gene related adverse events, which supports the initiation of more large scaled clinical trials to evaluate whether vascular growth factor therapy either as a gene or recombinant slow-release protein formulation therapy could be a new treatment modality to patients with severe coronary artery disease, which cannot be treated with conventional revascularization

Keywords: gene therapy, Vascular Growth Factors, angiogenesis, ischemic heart, review, VEGF, FGF, stem cell

Abbreviations: Ad.: Adenovirus; CABG: Coronary by-pass grafting; FGF: Fibroblast growth factor; i.c: Intra-coronary; i.m.: Intramyocardial; i.v.: Intra-venous; M.c.: Sustained release heparin-alginate FGF2 microcapsules; MRI: Magnetic Resonance Imaging investigation; PCI: Percutaneous coronary intervention; Pl.: Plasmid; SPECT: Single Photon Emission Computerized Tomography; VEGF: Vascular endothelial growth factor

Correspondence to: Jens Kastrup MD, DMSc, Associate professor, Cardiac Catheterization Laboratory 2014, The Heart Centre, University Hospital Rigshospitalet, DK-2100 Copenhagen 0, Denmark. Phone: +45 3545 2817, Fax: +45 3545 2805. E-mail: [email protected]

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