[Angiogenesis and vasculogenesis. Therapeutic strategies for stimulation of postnatal neovascularization]

Abstract

The formation of new blood vessel is essential for a variety of physiological processes like embryogenesis and the female reproduction as well as wound healing and neovascularization of ischemic tissue. Major progress in understanding the underlying mechanisms regulating blood vessel growth has offered novel therapeutic options in the treatment of a variety of diseases including ischemic cardiovascular disorders. Vasculogenesis and angiogenesis are the mechanisms responsible for the development of the blood vessels. Angiogenesis refers to the formation of capillaries from preexisting vessels in the embryo and adult organism. While pathologic angiogenesis includes the role of post-natal neovascularization in the pathogenesis of arthritis, diabetic retinopathy, and tumor growth and metastasis, therapeutic angiogenesis, either endogenously or in response to administered growth factors, includes the development of collateral blood vessels in tissue ischemia. Preclinical studies established that angiogenic growth factors could promote collateral artery development in animal models of peripheral and myocardial ischemia. Subsequent clinical trials using gene transfer of naked DNA encoding for VEGF for the treatment of critical limb and myocardial ischemia documented the safety and clinical benefit of this novel therapeutic approach. Several objective methods indicated marked improvement in collateral vessel development. Vasculogenesis describes the development of new blood vessels from in situ differentiating endothelial cells. Recently considered to be restricted to embryogenesis, there exists now striking evidence that endothelial progenitor cells (EPC) circulate also in adult peripheral blood able to participate in ongoing neovascularization. Different cytokines and growth factors have a stimulatory effect on these bone-marrow derived EPC. Granulocyte macrophage colony stimulating factor (GM-CSF) and vascular endothelial growth factor (VEGF) mobilize EPC from the bone marrow into the peripheral circulation. While their endogenous contribution to postnatal neovascularization needs to be documented, the iatrogenic expansion and mobilization of EPC might represent an effective means to augment the resident population of endothelial cells (ECs). This kind of cell therapy for tissue regeneration in ischemic cardiovascular diseases opens a novel and challenging clinical option besides or in addition to the use of growth factors in gene therapy.