Pathophysiological mechanisms of angiogenesis.

The growth of new blood vessels may be either beneficial or harmful. The angiogenic process may be measured by a variety of techniques, although it may often be the quality rather than quantity of resulting blood vessels that determines function. Endothelial cells play a key role in the initiation of angiogenesis, and vascular endothelial growth factor (VEGF) may be viewed as a prototypical direct-acting angiogenic factor. VEGF acts through multiple cell surface receptors and signaling pathways to stimulate endothelial cell proliferation, survival, and migration. By inducing other growth factor expression, VEGF stimulates a cascade of angiogenic activity. Different tissues may utilize various angiogenic pathways that are modulated by diverse host tissue responses. Furthermore, a single tissue may progress through a sequence of angiogenic pathways, for example, as acute injury progresses to chronic inflammation. The phenotype of the resulting neovasculature is critically dependent on the context in which it is formed. Biomarkers of angiogenesis are being developed as an aid to assessing human disease. Histological assessment of vascular density and angiogenic factor expression, in vivo imaging, Doppler ultrasound, and biofluid assays each may have clinical utility. Therapeutic targeting of angiogenesis will depend both on the generation of acceptable pharmacological agents and on the identification of patients who may and do gain benefit from such treatments.