title: Neuropeptide Y receptors in carotid plaques of symptomatic and asymptomatic patients: effect of inflammatory cytokines.
abstract: OBJECTIVE
  Cytokines released by the immune cells at the site of plaque milieu induce smooth muscle cell apoptosis to promote plaque instability. But, neuropeptide Y (NPY), a pleotropic factor, may modulate the effects of cytokines in atherosclerotic plaques of patients with carotid stenosis. Our aim was to investigate the relative expression of NPY-Y1, NPY-Y2 and NPY-Y5 receptors on carotid plaque vascular smooth muscle cells (pVSMCs) of symptomatic (S) and asymptomatic (AS) patients and examine the effect of inflammatory cytokines on the expression of NPY receptors, that may attenuate plaque rupture.
  
  
  RESULTS
  In healthy carotid artery, there were significantly increased immunopositivity and increased mRNA transcripts of NPY-Y1 and NPY-Y5 receptors in thin sections and isolated VSMCs, respectively, compared to S and AS plaques. However, the NPY-Y2 expression was higher in S and AS pVSMCs than controls. Stimulation of the cells with TNF-α, IL-12 or IFN-γ (50 ng/ml) decreased mRNA transcripts of NPY-Y1 and NPY-Y5 and increased NPY-Y2 mRNAs in VSMCs of healthy carotid artery. The effect of the cytokines on mRNA transcripts of NPY-Y5 and NPY-Y2 in pVSMCs of S and AS patients was similar to healthy VSMCs, but with variable effect on NPY-Y1.
  
  
  CONCLUSIONS
  Increased expression of NPY-Y2 receptors in symptomatic pVSMCs than in healthy and asymptomatic subjects suggests a potential role of NPY-Y2 in plaque instability. This is further supported by the pronounced effect of atheroma-associated cytokines to increase NPY-Y2 mRNA transcripts in pVSMCs of patients with carotid stenosis.
authors.affiliation: Center for Clinical and Translational Science, Creighton University School of Medicine, 2500 California Plaza, Omaha, NE 68178, USA.
authors.forename: Divya
authors.initials: D
authors.lastname: Pankajakshan
authors.forename: Guanghong
authors.initials: G
authors.lastname: Jia
authors.forename: Iraklis
authors.initials: I
authors.lastname: Pipinos
authors.forename: Steve H
authors.initials: SH
authors.lastname: Tyndall
authors.forename: Devendra K
authors.initials: DK
authors.lastname: Agrawal
mesh_terms: D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology; D016893:Carotid Stenosis / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D017476:Receptors, Neuropeptide Y / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C095889:neuropeptide Y2 receptor; C100568:neuropeptide Y5 receptor