Angiogenesis therapy in ischemic disease.
The ability of organisms to spontaneously develop collateral vessels represents an important response to vascular occlusive diseases that determines the severity of residual tissue ischemia. Neovascularization of ischemic cardiac or skeletal muscle may be sufficient to preserve tissue integrity and/or function, and may thus be considered to be therapeutic. Innovative gene technologies and advances in animal modeling have enabled research scientists to develop therapeutic angiogenesis strategies applied in animal models of limb or myocardial ischemia and in treatment of patients with peripheral vascular obstruction or coronary artery diseases. Several therapeutic strategies have been proposed and tested even at the clinical level. Recent studies have established the feasibility of using recombinant angiogenic growth factors (mainly VEGF and FGF) to enhance angiogenesis in patients with limb or myocardial ischemia. Angiogenesis therapies using cells as a support for growth factor delivery or using endothelial progenitor cells which may directly participate in the angiogenic process have also been developed. Finally, one potential alternative strategy may be the use of drugs with pro-angiogenic activity, available in an oral formulation and which are currently administered to patients for treatment of different pathologies. All strategies of angiogenesis therapy currently being tested have the potential to be effective in the treatment of ischemic disease. However, such strategies may cause harmful side effects which emphasize the need to be aware of the biological effects of each angiogenic agent proposed for clinical studies.
Silvestre
J S
JS
INSERM U541, hôpital Lariboisière, institut fédératif de recherche circulation-Paris 7, université Paris 7-Denis Diderot, 75475 Paris.
Lévy
B I
BI
D000284:Administration, Oral; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000494:pharmacology* / Q000627:therapeutic use; D015316:Genetic Therapy; D006801:Humans; D007249:Inflammation; D017202:Myocardial Ischemia / Q000188:drug therapy*; D018919:Neovascularization, Physiologic; D016491:Peripheral Vascular Diseases / Q000188:drug therapy; D013234:Stem Cells
D000806:Angiotensin-Converting Enzyme Inhibitors; D016228:Endothelial Growth Factors