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Tuesday, May 20, 2008

Therapeutic Angiogenesis

strategy is designed to promote the development of supplemental collateral blood vessels that will act as endogenous bypass conduits
Promotion of coronary collateral growth has many attractive features, particularly in
patients with angina who are not indicated for percutaneous coronary intervention or coronary artery
bypass grafting surgery.
Two major avenues:
1. gene therapy (the introduction of new genetic material into somatic cells to synthesize proteins that are
missing, defective, or desired for specific therapeutic purposes)
2. protein-based therapy
(administration of the growth factors, instead of the genes encoding for the growth factors responsible for angiogenesis).

Delivery of angiogenic factors (Protein-based therapy with cytokines including vascular endothelial growth factor and fibroblast growth factor) demonstrated functionally significant angiogenesis in several animal models.
Delivery of gene encoding for the respective protein product has been shown to induce angiogenesis in numerous
animal models, and expression of a functioning product has been demonstrated with evidence of
neovascularization and improved perfusion in the target myocardium.

Various early clinical
trials of therapeutic angiogenesis have shown reduction in anginal symptoms and increases in exercise
time, as well as objective evidence of improved perfusion, left ventricular function and angiographic
appearance following such angiogenic treatments.

Patients with chronic critical limb ischemia
who are not candidate for surgical or percutaneous revascularization- Therapeutic angiogenesis, which has the goal to achieve the process of new
blood vessel formation via the administration of growth factors, has become a new promising hope. The
discovery of the possibility of inducing sprouting of new vessels from preexisting vasa (angiogenesis) or
the in situ differentiation of endothelial cells from stem cell precursors (vasculogenesis) have open new
lease on life. In experimental studies therapeutic angiogenesis has been produced by
recombinant growth-factor protein application as well as by growth factor gene therapy. Most widely
studied factors belong to vascular endothelial growth factor (VEGF) or fibroblast growth factor (FGF)
families. Studies have also shown that, angiogenic growth factors stimulate endothelial cell migration
and accelerate endothelial repair by enhancing post-injury re-endothelization.

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