This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 25/10/2075    most recent 01.ATV.0000179601.19888.19v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Li, L. Articles by Zukowska, Z. Search for Related Content PubMed PubMed Citation Articles by Li, L. Articles by Zukowska, Z. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Substance via MeSH Medline Plus Health Information Angioplasty Related Collections Remodeling Restenosis Restenosis Pathophysiology Growth factors/cytokines Hypertension - basic studies Smooth muscle proliferation and differentiation Autonomic, reflex, and neurohumoral control of circulation Platelets Mechanism of atherosclerosis/growth factors

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:2075.)
© 2005 American Heart Association, Inc.

Vascular Biology

Chronic Stress Induces Rapid Occlusion of Angioplasty-Injured Rat Carotid Artery by Activating Neuropeptide Y and Its Y1 Receptors

Lijun Li; Ann-Cathrine Jönsson-Rylander; Ken Abe; Zofia Zukowska

From the Department of Physiology and Biophysics (L.L., K.A., Z.Z.), Georgetown University Medical Center, Washington DC; and AstraZeneca (A.-C.J.-R.), Mondal, Sweden.

Correspondence to Zofia Zukowska, Department of Physiology and Biophysics, Georgetown University, 3900 Reservoir Rd, Box 571460, Washington, DC 20057. E-mail zzukow01{at}georgetown.edu

Objective— We reported previously that neuropeptide Y (NPY) induces an atherosclerotic-like lesion that is significantly reduced by NPY-Y1 and NPY-Y5 receptor (R) inhibitors. Because antagonists also inhibit neointima induced by angioplasty alone, we now test whether stress-induced endogenous NPY release mimic these changes.

Methods and Results— Rats were nonstressed or stressed (4°C water; 2 hours per day for 14 days) starting immediately before and continuing after carotid artery angioplasty. Stress acutely and chronically increased blood pressure and doubled plasma NPY levels. After 14 days, angioplasty-induced neointima was markedly greater in stressed (than nonstressed) rats, in which most of the vessels became occluded with an atherosclerotic-like lesion containing macrophages, lipids, thrombus, and microvessels that was similar but more inflammatory than the injury in the NPY-treated vessels. Fourteen days after angioplasty combined with stress or NPY, Y1R and Y5R (mRNA and protein) became upregulated in areas of neointima, microvessels, and macrophages in injured carotid arteries. Stress- and NPY-induced changes were completely prevented by a selective Y1R antagonist (0.02 µmol/kg per minute for 14 days), whereas neointima induced by angioplasty alone was reduced by 60%.

Conclusions— Because of sympathetic NPY release, stress may be a less-than-appreciated risk factor for restenosis/atherosclerosis, and Y1R antagonists a potential therapy for these conditions.

Cold-stress or exogenous neuropeptide Y (NPY) induces rapid occlusion of angioplasty injured carotid artery with an atherosclerotic-like lesion, both of which are prevented after infusion of an NPY Y1 receptor antagonist. Thus, NPY Y1 receptor antagonist treatment could represent a future therapeutic target to treat atherosclerosis and restenosis.

Key Words: stress • neuropeptide Y • Y1 receptor antagonist • atherosclerosis • angioplasty