The molecular control of angiogenesis.

Angiogenesis is a key event in a broad range of pathological conditions including both diseases with an enhanced and insufficient angiogenesis. Angiogenesis is often initiated with vasodilation accompanied by an increase in vascular permeability. After destabilization of the vessel wall and degradation of the surrounding extracellular matrix, extravasation of plasma proteins provides a provisional scaffold for the migration of endothelial cells. Endothelial cell proliferation and migration themselves are under tight control by a balance of angiogenesis inducers and inhibitors. A large number of angiogenic factors work together in a highly coordinated manner to induce endothelial cell outgrowth and the formation of functional vessels. On the other hand, angiostatic factors may play a critical role in the pathogenesis of ischemic diseases and contribute to the termination of physiological angiogenesis. Angiogenesis ends with the recruitment of pericytes and smooth muscle cells, which stabilize the newly formed vessel. The rapid increase in the knowledge about the molecular mechanisms of angiogenesis has led to first treatment trials in diseases with both enhanced and reduced angiogenesis. Although initial results are promising, much more work has to be done to consider anti-angiogenic or pro-angiogenic approaches as reliable therapeutic tools.