Therapeutic angiogenesis for myocardial ischemia revisited: basic biological concepts and focus on latest clinical trials.

Therapeutic angiogenesis is based on the premise that the development of new blood vessels can be augmented by exogenous administration of the appropriate growth factors. Over the last years, successful preclinical studies and promising results of early clinical trials have created great excitement about the potential of therapeutic angiogenesis for patients with advanced ischemic heart disease. The authors provide an overview of the biology of angiogenesis, the basic characteristics of angiogenic factors, and the different routes of their delivery. They discuss experimental studies in animal models of myocardial ischemia and outline available clinical studies on therapeutic angiogenesis for myocardial ischemia. Related safety issues are also addressed followed by a critical perspective about the future of proangiogenic therapies for ischemic cardiovascular disorders. Despite the established proof of concept and reasonable safety, however, results of the latest trials on therapeutic angiogenesis for myocardial ischemia have provided inconsistent results and the definite means of inducing clinically useful therapeutic angiogenesis remain elusive. More studies are required to gain further insights into the biology of angiogenesis and address pharmacological limitations of current approaches of angiogenic therapy. The authors hope and envisage that in the not-too-distant future, these investigative efforts will lead to important new strategies for treatment of myocardial ischemic syndromes. Means of non-invasive individualized pharmacological therapeutic neovascularization may be the next major advance in the treatment of ischaemic heart disease.