Recent studies indicate that, in addition to its neuropoietic actions, brain derived neurotrophic factor (BDNF) promotes endothelial cell survival and induces neoangiogenesis in ischemic tissues. Unlike many vascular growth factors that act on many vascular beds, BDNF activity is relatively restricted to central arteries and cardiac skeletal muscle, skin and vasculature. Studies of newly described biological mediators that act on large vessel and microvascular beds in these organs will help us to better understand organ-specific vascular development as well as to develop novel therapeutic strategies to improve the condition of patients with cardiac and peripheral vascular disease. In this review we summarize dual pro-angiogenic actions of BDNF, which through local activation of TrkB receptor expressed on a sub-population of endothelial cells (ECs) and additionally by recruitment of bone marrow-derived cells, contribute to neoangiogenesis.
Importance of endothelial cells in angiogenesis.The development of a mature vascular bed is a complex and dynamic process, characterized by the coordinated proliferation and recruitment of endothelial and smooth muscle cells and subsequent patterning into capillaries, arteries and veins. It is controlled by locally produced growth factors, adhesion molecules and proteinases (Carmeliet 2000) that establish the primary vascular plexus consisting of endothelial cells. Subsequently, accessory cells such as pericytes and smooth muscle cells are recruited to sculpt the vasculature, by pruning and remodeling. During adulthood, the maintenance of blood vessels is further promoted by a combination of growth factors, cell:matrix interactions and shear stress forces. The molecular mechanisms that are utilized during development to sculpt the immature vascular bed may be utilized during the adaptive neovascularization of the heart that occurs as a consequence of cardiac ischemia.Endothelial cells, comprising the inner layer of cells of the vasculature, are the main regulators of vascular homeostasis. They play important roles in the physiology and maintenance of vascular integrity and tone, as well as in pathological situations such as inflammation and tumor angiogenesis. Although endothelial cells exhibit many common morphological characteristics, they display significant heterogeneity in different organs, to promote organ-specific functions (Garlanda and Dejana 1997). While coronary arteries nourish the myocardium, the highly specialized endothelial cells in the bone marrow sinusoids are intimately involved in the homing of hematopoietic progenitors and play an important role in maturation, proliferation and trafficking of those cells to the blood circulation. These characteristics may be endowed by organ-specific growth factors secreted by parenchymal cells in a paracrine manner.The healthy endothelium is both anti-coagulant and anti-thrombotic, by expressing or secreting numerous proteins that regulate blood coagulation and platelet activation (Robson et al.