Neuropeptide Y: a novel mechanism for ischemic angiogenesis.

Sympathetic nerve activation often accompanies tissue ischemia, which in turn stimulates angiogenesis, but whether the nerves regulate vascular functions beyond vasoconstriction (i.e., by promoting new vessel formation) has never been established. Neuropeptide Y (NPY) is a sympathetic cotransmitter preferentially released during intense or prolonged stress, which causes vasoconstriction and vascular smooth muscle cell proliferation by activating multiple Gi/o-coupled receptors, Y1 and Y5. At nonvasoconstrictive concentrations and through non-Y1 receptors, NPY also stimulates endothelial cell adhesion to matrix, migration, proliferation, capillary tube formation on matrigel, and aortic sprouting. Recent studies also indicate that NPY and its non-Y1 receptors exert powerful angiogenic effects in peripheral limb ischemia, promising a new way of treatment for revascularization of ischemic tissues.