on April 10, 2003
Published online before print April 10, 2003, doi: 10.1161/01.ATV.0000071349.30914.25
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Submitted on February 26, 2003
Accepted on March 21, 2003
Neuropeptide Y-Induced Acceleration of Postangioplasty Occlusion of Rat Carotid Artery
Lijun Li ;
From the Department of Physiology and Biophysics, Georgetown University, Washington, DC.
* To whom correspondence should be addressed. E-mail: zzukow01{at}georgetown.edu.
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.
Methods and 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 µg/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 µg 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.
Key words: neuropeptide Y • NPY receptors • angioplasty • atherosclerosis • restenosis • neointima • platelets
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