Angiogenesis gene therapy to rescue ischaemic tissues: achievements and future directions

Ischaemic diseases are characterized by an impaired supply of blood resulti ng from narrowed or blocked arteries that starve tissues of needed nutrient s and oxygen. Coronary-atherosclerosis induced myocardial infarction is one of the leading causes of mortality in developed countries. Ischaemic disea se also affects the lower extremities. Considerable advances in both surgic al bypassing and percutaneous revascularization techniques have been reache d. However, many patients cannot benefit from these therapies because of th e extension of arterial occlusion and/or microcirculation impairment. Conse quently, the need for alternative therapeutic strategies is compelling. An innovative approach consists of stimulating collateral vessel growth, a nat ural host defence response that intervenes upon occurrence of critical redu ction in tissue perfusion (Isner & Asahara, 1999). This review will debate the relevance of therapeutic angiogenesis for promotion of tissue repair. T he following issues will receive attention: (a) vascular growth patterns, ( b) delivery systems for angiogenesis gene transfer, (c) achievements of the rapeutic angiogenesis in myocardial and peripheral ischaemia, and (d) futur e directions to improve effectiveness and safety of vascular gene therapy.