VEGF promotes vascular sympathetic innervation.
The sympathetic nervous system, via postganglionic innervation of blood vessels and the heart, is an important determinant of cardiovascular function. The mechanisms underlying sympathetic innervation of targets are not fully understood. This study tests the hypothesis that target-derived vascular endothelial growth factor (VEGF) promotes sympathetic innervation of blood vessels. Western blot and immunohistochemical analyses indicate that VEGF is produced by vascular cells in arteries and that VEGF receptors are expressed on sympathetic nerve fibers innervating arteries. In vitro, exogenously added VEGF and VEGF produced by vascular smooth muscle cells (VSMCs) in sympathetic neurovascular cocultures inhibited semaphorin 3A (Sema3A)-induced collapse of sympathetic growth cones. In the absence of Sema3A, VEGF and VSMCs also increased growth cone area. These effects were mediated via VEGF receptor 1. In vivo, the neutralization of VEGF inhibited the reinnervation of denervated femoral arteries. These data demonstrate that target-derived VEGF plays a previously unrecognized role in promoting the growth of sympathetic axons.
Marko
Stephen B
SB
Department of Pharmacology, University of Vermont, Burlington, Vermont, USA.
Damon
Deborah H
DH
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002478:Cells, Cultured; D018920:Coculture Techniques; D005263:Femoral Artery / Q000294:innervation* / Q000378:metabolism; D020439:Growth Cones / Q000378:metabolism; D007150:Immunohistochemistry; D009131:Muscle, Smooth, Vascular / Q000294:innervation* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D039942:Neuropilin-1 / Q000378:metabolism; D019899:Paracrine Communication; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000378:metabolism; D040121:Semaphorin-3A / Q000378:metabolism; D017783:Superior Cervical Ganglion / Q000378:metabolism; D013562:Sympathectomy; D017779:Sympathetic Fibers, Postganglionic / Q000378:metabolism* / Q000601:surgery; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D011994:Recombinant Proteins; C108639:SEMA3A protein, human; D040121:Semaphorin-3A; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D039942:Neuropilin-1; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2