VEGF therapy: a timely retreat

Abstract

The formation of new blood vessels is required for the onset and progression of many biological processes during embryonic development and into adulthood. Excessive neovascularization contributes to the pathogenesis of disorders such as tumour growth, chronic inflammation, and vascular retinopathies. On the other hand, an inadequate blood supply is a determining factor in the progression of tissue damage in ischaemic processes.1 In spite of the continuous efforts at prevention, brain and heart ischaemia as an end consequence of atherosclerosis is still a major cause of morbidity and mortality in western countries. A major challenge in cardiovascular research today is to improve revascularization of ischaemic tissues through the development of new treatments that can either substitute high-risk surgical procedures or be used as an adjuvant treatment. The increasing knowledge on the intricate mechanisms that regulate neovascularization has allowed the design of new therapies based on the administration of proangiogenic factors such as VEGF-A, FGF-1, -2 and -4, HGF, and Del-1 (therapeutic angiogenesis).2 A variety of approaches have been used to deliver proangiogenic factors to ischaemic tissues. Direct administration of recombinant factors (protein therapy) allows strict dose control; however, the maintenance of effective concentrations over prolonged periods is hard to achieve. Gene therapy with non-viral vectors, such as naked plasmid DNA, has a low transduction efficiency and the duration of transgene expression is limited. An alternative option is gene therapy with viral vectors, which provide higher levels of transduction and protein expression. The choice of viral vector will depend on the particular application; nevertheless, vector-specific characteristics related to transduction efficiency and biological safety … *Corresponding author. Tel: +34 91 4531200; fax: +34 91 453 1265. E-mail address : aalfranca{at}cnic.es