Growth factor-induced therapeutic neovascularization for ischaemic vascular disease: time for a re-evaluation?

Abstract

Therapeutic angiogenesis and arteriogenesis represent an alternative treatment modality for patients with advanced ischaemic coronary or peripheral artery occlusive disease, who are unsuitable for standard revascularization procedures. Proof-of-concept evidence for therapeutic growth factor, both gene and protein-mediated neovascularization was provided in animal models of chronic myocardial and hindlimb ischaemia. Early human, phase I, trials utilizing the prototypical growth factor families, vascular endothelial growth factor and fibroblast growth factor, documented safety and suggested improvements in anginal symptoms and functional status. Large, randomized, placebo-controlled phase II/III clinical trials have, however, yielded variable results as such studies have suffered from significant limitations in therapeutic approach or design, which limits the ability to draw firm conclusions. Future trials must incorporate robust delivery strategies and address issues of study design including proper patient selection. Laboratory-based refinements in therapy, including a focus on the promotion of arteriogenesis and the modification of patient 'endotheliopathy', will all further enhance the potential of therapeutic neovascularization strategies.