I. Strategies
II. Clinical Application
III. Clinical Trials
IV. Adverse Outcomes
GLOSSARY
angina pectoris short duration, recurrent chest pain or pressure often accompanied by feelings of suffocation and impending doom; most frequently associated with lack of blood and oxygen to the heart muscle.
arterioles small branches of arteries.
atherosclerosis same as atheroma, raised plaques filled with cholesterol, calcium, and other substances on the inner wall of arteries that obstruct the lumen and the flow of blood; the plaque of atheroma hardens the artery, hence the term atherosclerosis (sclerosis ¼ hardening).
capillaries fine, thin-walled blood vessels that branch from arterioles and feed the tissues and cells with blood and fluids.
ischemia temporary lack of blood and oxygen to an area of cells, for example, the heart muscle, usually due to severe obstruction of the artery supplying blood to this area of cells.
myocardial infarction death of an area of heart muscle due to blockage of a coronary artery by blood clot and atheroma; medical term for a heart attack or coronary thrombosis.
myocardium the heart muscle.
ANGINA PECTORIS IS A FRUSTRATING PROBLEM for both the patient and the cardiologist. It is refractory to optimal medical therapy and not amenable to revascular-ization procedures that include percutaneous coronary interventions (PCI) such as balloon angioplasty with intracoronary stents and coronary artery bypass graft (CABG) surgery. Alternative strategies for improving blood flow to the myocardium include transmyocardial laser revascularization, but it has not proved successful. Gene therapy including the use of angiogenic peptides is another possible therapy. A major goal of gene therapy and the use of antigenic peptides is the production of therapeutic angiogenesis, or functional new blood vessel growth in the myocardium. It is hoped that this should improve myocardial oxygen supply. Gene therapy has yet to show convincing efficacy in humans and the therapy may even be harmful.

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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.