ABSTRACT
Tissue ischemia and the arterial blood supply..................................... 253 Therapeutic agents: growth factors and cells ....................................... 254 Clinical trials: coronary artery disease (CAD)...................................... 255 Clinical trials: peripheral arterial disease (PAD).................................. 257 Problems with trials: patient selection and placebo effect ................. 257 Potential safety issues of therapeutic angiogenesis ............................. 258 Monitoring and assessment of angiogenesis ........................................ 259 Master switch genes and second generation angiogenic factors....... 261 Therapeutic agent delivery: site of delivery ......................................... 261 Therapeutic agent delivery: mode of delivery ..................................... 262 Summary ..................................................................................................... 263 References.................................................................................................... 263
Tissue ischemia and the arterial blood supply Deprivation of oxygen and nutrients limits tissue viability and function. The natural response to tissue ischemia includes the local up-regulation of angiogenic growth factors, coupled with the mobilization and recruitment of circulating cellular elements that facilitate the development of new vasculature. In many circumstances, however, this endogenous response is not sufficient to fully meet the metabolic needs of compromised tissues, resulting in symptoms of ischemia. The attempt to augment this natural revascularization response has been termed therapeutic angiogenesis and has primarily involved the administration of growth factors and, more recently, cellular products.1
