Therapeutic Angiogenesis Using Basic Fibroblast Growth Factor and Vascular Endothelial Growth Factor Using Various Delivery Strategies.
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Therapeutic angiogenesis is a novel technique that may provide a treatment strategy for ischemic heart diseasepatients who are not candidates for standard revascularization procedures. It works by promoting the growth of blood vessels provide new venues for blood flow. Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) are the most widely studied angiogenic agents. They have been shown to induce functionally significant angiogenesis in various animal models of chronic myocardial ischemia using various delivery strategies. Preclinical and clinical studies using these growth factors are reviewed with an emphasis on the different delivery strategies,including intracoronary and intravenous delivery; left atrial injections; intrapericardial administration; local intravascular and perivascular delivery; and intramyocardial delivery using single bolus delivery, repeated administration, gene therapy, and sustained delivery. Although intracoronary and intravenous delivery may be preferred for their ease of use and their applicability to a large patient population, systemic recirculation and lack of sustained tissue exposure to these therapeutic agents may limit the usefulness of this approach. Intrapericardial and intramyocardial administration, sustained local delivery, and second-generation gene therapy vectors may allow a safer and more sustained administration and may be preferable for clinical use. However, only well-designed randomized, double-blind placebo-controlled trials using outcome measures tailored to myocardial angiogenesis will determine the feasibility and effectiveness of this treatment modality.