Angiogenesis must be distinguished from arteriogenesis. Angiogenesis is the formation of new vessels that lack a tunica media; arteriogenesis describes nature’s phenom¬enon of newly formed arterioles with fully developed tunica media. A prime example of arteriogenesis is collateral vessels observed angiographically in patients with severe obstructive coronary artery disease (ischemic heart disease) or long-standing peripheral vascular disease. An example of angiogenesis is the formation of thin-walled fragile capillaries along the borders of a myocardial infarct. The formation of strong arterioles with a normal media is an acceptable goal that may never materialize.

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• I. STRATEGIES
  Gene therapy involves either the delivery of whole active genes (gene transfer) or the blockade of native gene expres¬sion by transfection of cells with short chains of nucleic acids (oligonucleotides). These short, single-stranded DNA molecules are used as drugs to target the inactivation of mRNA- or DNA-binding proteins.
• II. CLINICAL APPLICATION
  Gene therapy remains a daunting task. Table 2 lists the pertinent cardiac conditions. There has been no clinical trial for heart failure or transplantation. Presently impro¬ved oxygen supply to a myocardium deprived of oxygen because of atheromatous coronary artery obstruction is the goal. Success has thus far not been obtained. In addition this goal is fraught with danger, because angiogenesis may increase plaque growth and decrease the thickness of the fibrous plaque which is protective and fragile. New vessels within the plaque are prone to rupture causing ultimate plaque rupture and severe cardiac events, see Section IV.
• III. CLINICAL TRIALS A. The Euroinject
  One trial was presented at the American College of Cardiology scientific session in March of 2003. This multinational study, however, involved only 80 patients. Patients with end-stage refractory angina with severe ischemic heart disease not amenable to all forms of revascularization therapy were randomized. Patients with recent myocardial infarction or proliferative retinopathy were excluded.
• BIBLIOGRAPHY
  Cappell, D. F. In Muir’s Textbook of Pathology, seventh ed. Edward Arnold Ltd., London, 1958.