Sympathetic nervous system-targeted neuropeptide Y overexpression in mice enhances neointimal formation in response to vascular injury.
Sympathetic neurotransmitter neuropeptide Y (NPY) is associated with vascular remodelling, neointimal hyperplasia and atherosclerosis in experimental animal models and clinical studies. In order to study the role of sympathetic nerve-produced NPY in vascular diseases, transgenic mouse model overexpressing NPY in central and peripheral noradrenergic neurons under the dopamine-beta-hydroxylase (DBH) promoter was recently created (OE-NPY(DBH) mouse). This study aimed to examine the effect of NPY overexpression on arterial neointimal hyperplasia in an experimental model of vascular injury. Transgenic OE-NPY(DBH) mice and wildtype control mice of two different inbred strains (C57BL/6 and FVB/n) underwent a femoral artery surgery with a transluminar injury by a 0.38-mm guide wire insertion. Arteries were harvested 4 weeks from the surgery, and they were stained for basic morphology. Both strains of OE-NPY(DBH) mice, as compared with wildtype control mice, showed on average 50% greater formation of the neointima (P<0.01) and an increase in the medial area (P=0.05). The results suggest that moderately increased neuronal NPY causes the arteries to be more susceptible to femoral artery thickening after endothelial injury. The OE-NPY(DBH) mouse provides a novel tool to explore the role of NPY in the development of vascular disease related to metabolic disorders.
Ruohonen
Suvi T
ST
Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Finland. suvi.ruohonen@utu.fi
Abe
Ken
K
Kero
Mia
M
Toukola
Laura
L
Ruohonen
Saku
S
Röyttä
Matias
M
Koulu
Markku
M
Pesonen
Ullamari
U
Zukowska
Zofia
Z
Savontaus
Eriika
E
D000818:Animals; D005263:Femoral Artery / Q000293:injuries*; D051379:Mice; D008810:Mice, Inbred C57BL; D009478:Neuropeptide Y / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000378:metabolism*; D019076:Transgenes; D017539:Tunica Intima; D001616:beta-Galactosidase / Q000235:genetics
D009478:Neuropeptide Y; D001616:beta-Galactosidase