Therapeutic angiogenesis and vasculogenesis for ischemic disease. Part I: angiogenic cytokines.

Deprivation of oxygen and nutrients provides a serious threat for tissue viability. Nature’s response to the development of profound tissue ischemia includes the upregulation of angiogenic growth factors and mobilization of circulating cellular elements that together enable development of an accessory vasculature.1 The involved paradigm, not surprisingly, recapitulates many aspects of embryonic circulatory development. Multiple angiogenic factors and inhibitors have been implicated in the formation and correct patterning of functional blood vessels. Although hampered by several ambiguous clinical trials, transfer of genes encoding for proangiogenic factors is still an important therapeutic option to induce vascular growth after critical ischemia. Recent studies provide further evidence that neovascularization is regulated by infiltrating circulation cells, including bone marrow–derived endothelial progenitor cells or inflammatory cells. The use of “cell therapy” for therapeutic vasculogenesis will be discussed in the second part of this review article.