Neuropeptide Y-induced acceleration of postangioplasty occlusion of rat carotid artery.
OBJECTIVE
Attempts to restore blood flow through atherosclerotic vessels by angioplasty often result in restenosis. Because the role of nerves in this process is unclear, we investigated whether neuropeptide Y (NPY), a sympathetic cotransmitter with vascular mitogenic activities, contributes to postangioplasty restenosis.


RESULTS
Carotid artery balloon angioplasty upregulated vascular expression of NPY and its processing enzyme (DPPIV/cd26) and receptors (Y1, Y2, Y5 mRNA and protein) within 6 to 24 hours and stimulated neointima formation and accumulation of NPY in platelets after 14 days. NPY pellets (1 to 10 microg/pellet for 14 days) inserted next to the injured artery elevated platelet and vascular NPY immunoreactivity to stress-like levels and dose-dependently augmented angioplasty-induced neointima. Strikingly, 10 microg NPY for 14 days led to vessel occlusion with an atherosclerotic-like lesion, with thrombus and neointima containing neovessels, macrophages, matrix, and lipids. Y1 or Y5 receptor antagonist completely prevented the effect of NPY and reduced angioplasty-induced neointima by 50%.


CONCLUSIONS
Angioplasty upregulates platelet and vascular NPY systems, which then contribute to neointima formation via Y1 and Y5 receptor activation. Increasing NPY to high stress levels triggers formation of a thrombotic atherosclerotic-like lesion and vessel occlusion. Thus, NPY may be a risk factor for accelerated atherosclerosis, and NPY receptor antagonists may be a possible new treatment for restenosis.
Li
Lijun
L
Department of Physiology and Biophysics, Georgetown University, Washington, DC 20057-1460, USA.
Lee
Edward W
EW
Ji
Hong
H
Zukowska
Zofia
Z
D000704:Analysis of Variance; D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology* / Q000628:therapy; D001792:Blood Platelets / Q000378:metabolism; D017536:Carotid Artery, Common; D016893:Carotid Stenosis / Q000209:etiology* / Q000473:pathology / Q000628:therapy; D004730:Endothelium, Vascular / Q000473:pathology; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012008:Recurrence; D017539:Tunica Intima / Q000473:pathology; D015854:Up-Regulation
D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C095889:neuropeptide Y2 receptor; C100568:neuropeptide Y5 receptor