Myocardial ischemia and peripheral vascular disease persist as significant clinical problems despite improved medical, surgical, and endovascular therapies. Advances in our understanding of the biological mechanisms that govern capillary neovascularization and collateral artery growth have enabled molecular therapies for revascularizing ischemic tissues. Generally known as therapeutic angiogenesis, this review summarizes the essential pre-clinical research and the major clinical trials of molecular therapies for ischemic disease. Early clinical experience has established the proof of principle, however, inconsistent and modest improvements in clinical outcomes have exposed the complexity of neovascularization and problems with transitioning basic science to clinical applicability.
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