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


BACKGROUND
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.


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.
Lekas
Michael
M
Terrence Donnelly Heart Center, Vascular Biology Research Laboratory, Canada.
Lekas
Poli
P
Latter
David A
DA
Kutryk
Michael B
MB
Stewart
Duncan J
DJ
D043925:Angiogenesis Inducing Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000188:drug therapy / Q000628:therapy*; D001158:Arteries / Q000187:drug effects; D002986:Clinical Trials as Topic; D003327:Coronary Disease / Q000188:drug therapy / Q000628:therapy*; D005346:Fibroblast Growth Factors / Q000494:pharmacology / Q000627:therapeutic use*; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000628:therapy*; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000235:genetics; D016491:Peripheral Vascular Diseases / Q000188:drug therapy / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000627:therapeutic use; D012107:Research Design; D016896:Treatment Outcome; D042442:Vascular Endothelial Growth Factors / Q000494:pharmacology / Q000627:therapeutic use*
D043925:Angiogenesis Inducing Agents; D011994:Recombinant Proteins; D042442:Vascular Endothelial Growth Factors; D005346:Fibroblast Growth Factors