Abstract 12280: Peripheral Nerve is Critical for Vasa Vasorum Maturation in Injured Vascular Walls. -Effects of Substance P on Pericytes-Mediated Vascular Maturation
Immature vasa vasorum (VV) have been implicated to induce the formation of unstable plaques. Normalization of VV within plaque would be attractive therapeutic approach for acute coronary syndrome. Pericytes stabilize and enlarge neovessels, and muscular cells/pericytes-covered mature vessels obtains vasomotor properties with regeneration of peripheral nerve. It is reported that peripheral nerve also contributes to the vascular development. In the present study, we investigated the role of peripheral nerve on the formation of VV in injured vessels.
Methods and Results: Formation of VV was enhanced within 10 days after wire-mediated injury of femoral arteries of C57BL6 mice. We’ve developed new in vivo angiogenesis assay to estimate the formation of VV (Fig). Immunohistochemical analysis showed that peripheral nerve was already regenerated around the pre-matured VV. These findings suggest that peripheral nerves have alternative role on pre-matured VV beside vasomotor effects. Gelatin hydrogels releasing VEGF was applied around the injured vessel, and length and permeability of VV were further enhanced. When regeneration of peripheral nerve was stimulated by nerve growth factor, size in diameter of VV was enhanced and vascular permeability was reduced (Fig). NG2-positive pericyte cell lines (PCs) have been established from temperature sensitive SV40T antigen transgenic mice. Substance P (SP), one of neurotransmitters of peripheral nerve had potent proliferative effects on PCs. An ex vivo aorta ring assay demonstrated that SP did not enhance the length of microvessels sprouting from aorta explants. When aorta was co-cultured with PCs, the length and diameter of microvessels were enhanced and PCs were localized at peri-vascular sites. Importantly, SP enhanced the PCs-induced angiogenesis.
Conclusion: Regeneration of peripheral nerve enhances vascular stability and maturation of VV, and SP contribute to VV maturation through the action on pericytes.
- © 2011 by American Heart Association, Inc.