Deletion of neuropeptide Y (NPY) 2 receptor in mice results in blockage of NPY-induced angiogenesis and delayed wound healing

Abstract

Neuropeptide Y (NPY), a 36-aa peptide, is widely distributed in the brain and peripheral tissues. Whereas physiological roles of NPY as a hormone͞neurotransmitter have been well studied, little is known about its other peripheral functions. Here, we report that NPY acts as a potent angiogenic factor in vivo using the mouse corneal micropocket and the chick chorioallantoic membrane (CAM) assays. Unlike vascular endothelial growth factor (VEGF), microvessels induced by NPY had distinct vascular tree-like structures showing vasodilation. This angiogenic pattern was similar to that induced by fibroblast growth factor-2, and the angiogenic response was dose-dependent. (2). Although the neuropeptides were isolated and characterized several decades ago and the NPY receptor cDNAs have been cloned for 5-10 yr, surprisingly little is known about the molecular mechanisms that regulate NPY receptor activity and the biological significance of NPY in the periphery.It has been found that NPY regulates the vascular tone by inducing contractions of blood vessels (3). NPY also stimulates growth of vascular smooth muscle cell and hypertrophy of ventricular cardiomyocytes (4, 5). The trophic effect of NPY on blood vessels does not seem to be limited to vascular smooth muscle cells.

Regulation of scar formation by vascular endothelial growth factor

“…Stimulation of angiogenesis can enhance healing rates, [27][28][29][30][31][32][33] whereas a reduction in angiogenesis can impair the same. [34][35][36][37] The benefits of enhanced angiogenesis have primarily been shown in models of impaired wound healing 28,32,33 or severe injury. [29][30][31] In contrast, several reports have shown that modulation of angiogenesis does not affect epidermal healing rates or overall wound closure to a great degree, [38][39][40][41][42][43] and some studies have even reported enhanced healing with reduced angiogenesis.…”

Neuronal system-dependent facilitation of tumor angiogenesis and tumor growth by calcitonin gene-related peptide

“…These data suggest that during development, peripheral nerves have a role in determining the organ-specific patterns of blood vessel branching and arterial maturation (5). Furthermore, some neuronal factors such as Notch and neuropeptide Y were reported to have roles in tumor-associated angiogenesis (6,7).…”

The axonal attractant Netrin-1 is an angiogenic factor

“…Chorioallantoic membrane assay (CAM) was performed as described (28,29). Briefly, fertilized Leghorn chicken eggs were incubated under conditions of constant humidity (60%) at 37°C for 72 h. On days 3-4, eggs were opened into sterile clingwrap hammocks and incubated at 37°C with 2.0% CO 2 and 90% relative humidity for 4 more days.…”