Vascular Endothelial Growth Factor for Therapeutic Angiogenesis:Problems and Potential Solutions

Vascular endothelial growth factor (VEGF) is a major angiogenic factor involved in physiological as well as pathological angiogenesis.The ability of VEGF to promote angiogenesis in animal and clinical studies has been studied extensively.However,increasing evidence indicates that the new vasculature needs to be stabilized to avoid deleterious effects such as edema and hemangioma formation.Moreover,VEGF can promote angiogenesis but may also enhances atherosclerotic plaque progression.Mature vessels may be generated by modulating timing and dosage of VEGF expression,or by combination of 'growth' factors with 'maturation' factors like platelet derived growth factor BB (PDGF-BB).Cell-mediated gene transfer has unique characteristics that make it a useful tool for therapeutic angiogenesis.The combined insertion of different gene constructs into single cells and their progeny allows the simultaneous expression of different 'growth' and 'maturation' factors within the same cell.An alternative strategy is therapy based on transcription factors.