title: Neuropeptide Y-induced acceleration of postangioplasty occlusion of rat carotid artery.
abstract: 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.
authors.affiliation: Department of Physiology and Biophysics, Georgetown University, Washington, DC 20057-1460, USA.
authors.forename: Lijun
authors.initials: L
authors.lastname: Li
authors.forename: Edward W
authors.initials: EW
authors.lastname: Lee
authors.forename: Hong
authors.initials: H
authors.lastname: Ji
authors.forename: Zofia
authors.initials: Z
authors.lastname: Zukowska
mesh_terms: 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
chemical_list: D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C095889:neuropeptide Y2 receptor; C100568:neuropeptide Y5 receptor