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Therapeutic Angiogenesis

Pharmacology

  1. Mary E. Gerritsen

Published Online: 15 SEP 2006

DOI: 10.1002/3527600906.mcb.200500007

Reviews in Cell Biology and Molecular Medicine

Reviews in Cell Biology and Molecular Medicine

How to Cite

Gerritsen, M. E. 2006. Therapeutic Angiogenesis. Reviews in Cell Biology and Molecular Medicine. .

Author Information

  1. Exelixis, South San Francisco, CA

Publication History

  1. Published Online: 15 SEP 2006

Abstract

Therapeutic angiogenesis refers to the use of drugs or other therapeutic modalities to stimulate the revascularization of ischemic tissue. The concept was first introduced by the German gynecologist Michael Höckel in 1989 as a therapeutic approach to improve regional tissue perfusion and viability following surgery. In the intervening two decades, there has been a virtual explosion of information relating to the growth factors and receptors involved, the molecular mechanisms of new vessel formation, the development of numerous animal models, and a number of clinical trials. The two major clinical indications are the coronary artery (ischemic heart disease) and peripheral vascular disease, but therapeutic angiogenesis could also be applied to wound healing.

Ischemic heart disease is the leading cause of death and the major contributor to morbidity in the Western world. This problem will continue to grow as the population ages and will be even more severe if the “epidemics” of obesity, metabolic syndrome, and diabetes continue to develop unchecked. In the United States alone in 1999 there were 1.1 million percutaneous coronary revascularizing interventions, 355 000 coronary bypass surgeries, and 131 000 endarterectomies. Annually, about 1.2 million Americans will have a first or recurrent coronary attack and roughly 502 000 of these people will die −340 000 of them in an ER or before they reach a hospital. It is estimated that 7.8 million Americans aged 20 years and older have survived a heart attack and about 6.8 million Americans have angina pectoris (chest pain or discomfort due to reduced blood supply to the heart). Moreover, within six years of a recognized heart attack, 18% of men and 35% of women will have a second heart attack. A significant number of these patients will die or be disabled with heart failure or the aftermath of a stroke. In the United States, coronary heart disease is the number one cause of premature permanent disability (19% of total) in the labor force (American Heart Association Heart Disease and Stroke Statistics—2004 Update). Peripheral ischemic vascular disease is also a significant cause of major morbidity, affecting up to 14 to 18 million patients in the United States. In these patients, intermittent claudication (pain while walking that abates during rest) is the most common symptom. Other symptoms include numbness or weakness in the legs, aching pain in the feet or toes while at rest, nonhealing ulcers on the leg or foot, cold legs or feet, and skin color changes of the legs or feet. However, less than 20% of the patients with peripheral vascular disease have been diagnosed, and of those that are, many are often undertreated. Of these patients, more than 70% experience no change or any improvement in symptoms after 5 to 10 years of conservative management. However, 20 to 30% of patients develop more severe symptoms that require intervention, and a small fraction (less than 10%) will require amputation. Moreover, the 5 and 10-year rates of mortality can reach 30 and 50% respectively.

Keywords:

  • Angiogenesis;
  • Arteriogenesis;
  • Ischemia;
  • Myocardial Infarction;
  • Peripheral Vascular Disease (PVD);
  • Reperfusion;
  • Revascularization;
  • Therapeutic Angiogenesis;
  • Vasculogenesis