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Clinical Review Science, medicine, and the future

Therapeutic angiogenesis

BMJ 1999; 318 doi: (Published 05 June 1999) Cite this as: BMJ 1999;318:1536
  1. Timothy D Henry, director of interventional cardiology. (
  1. Cardiology Division, Hennepin County Medical Center, 701 Park Avenue, Minneapolis, MN 55415, USA

    Editorial by Brindle et al

    Therapeutic angiogenesis is the clinical use of growth factors to enhance or promote the development of collateral blood vessels in ischaemic tissue. Progress in understanding the process of angiogenesis, the isolation of angiogenic growth factors, successful preclinical studies, and promising early results in clinical trials have created great excitement about the potential of therapeutic angiogenesis.1 Although many questions remain, therapeutic angiogenesis may be the next major advance in the treatment of ischaemic heart disease.

    The clinical problem

    Ischaemic heart disease caused 6.3 million deaths worldwide in 1990, and it remains the leading cause of morbidity and mortality in the world.2 Advances in secondary prevention, reperfusion treatment for acute myocardial infarction, and revascularisation via coronary artery bypass graft surgery and percutaneous coronary interventions have improved long term survival of patients with established coronary heart disease. With these improvements in survival, and the ageing of populations, increasing numbers of patients are left with substantial myocardial ischaemia that is not amenable to revascularisation. Despite major advances in revascularisation techniques, these patients may constitute 5-15% of patients undergoing coronary angiography.

    Potential of therapeutic angiogenesis

    The importance of the coronary collateral circulation has become increasingly clear over the past 20 years.35 The coronary collateral circulation is a complex network of interconnecting vessels, most of which are <200 μm in diameter. Highly variable from patient to patient, this network develops from the recruitment of existing blood vessels as well as the creation of new vessels. The main stimulants for collateral growth are duration and severity of ischaemia, shear stress on the arterial wall, and inflammation.5 In acute myocardial infarction the presence of collateral circulation decreases infarct size, improves left ventricular function, decreases the likelihood of an aneurysm forming, and improves survival. 3 4 While collateral circulation may provide adequate coronary perfusion at …

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