title: Vascular neuropeptide Y contributes to atherosclerotic plaque progression and perivascular mast cell activation.
abstract: OBJECTIVE
  Neuropeptide Y is an abundantly expressed neurotransmitter capable of modulating both immune and metabolic responses related to the development of atherosclerosis. NPY receptors are expressed by a number of vascular wall cell types, among which mast cells. However, the direct effects of NPY on atherosclerotic plaque development and progression remain to be investigated. In this study we thus aimed to determine whether NPY is expressed in atherosclerotic plaques and to establish its role in atherosclerotic plaque development.
  
  
  RESULTS
  NPY expression was seen to be increased up to 2-fold in unstable human endarterectomy plaques, as compared to stable plaques, and to be significantly upregulated during lesion progression in apoE(-/-) mice. In apoE(-/-) mice focal overexpression of NPY in the carotid artery significantly increased atherosclerotic plaque size compared to controls, while plaque composition was unaffected. Interestingly, perivascular mast cell activation was significantly higher in the NPY-overexpressing mice, suggesting that NPY may impact plaque progression in part via mast cell activation. Furthermore, in vitro NPY-induced murine mast cell activation resulted in the release of pro-atherogenic mediators including IL-6 and tryptase.
  
  
  CONCLUSIONS
  Our data show that NPY expression is increased during atherogenesis and in particular in unstable plaques. Furthermore, perivascular overexpression of NPY promoted plaque development and perivascular mast cell activation, suggestive of a role for NPY-induced mast cell activation in lesion progression.
authors.affiliation: Division of Biopharmaceutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands. Electronic address: h.m.lagraauw@lacdr.leidenuniv.nl.
authors.forename: H Maxime
authors.initials: HM
authors.lastname: Lagraauw
authors.affiliation: Division of Biopharmaceutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
authors.forename: Marijke M
authors.initials: MM
authors.lastname: Westra
authors.affiliation: Division of Biopharmaceutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
authors.forename: Martine
authors.initials: M
authors.lastname: Bot
authors.affiliation: Division of Biopharmaceutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
authors.forename: Anouk
authors.initials: A
authors.lastname: Wezel
authors.affiliation: Division of Biopharmaceutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: van Santbrink
authors.affiliation: Laboratory of Experimental Cardiology, University Medical Center Utrecht, The Netherlands.
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
authors.affiliation: Experimental Vascular Pathology Group, Department of Pathology, Maastricht University Medical Center, The Netherlands.
authors.forename: Erik A L
authors.initials: EA
authors.lastname: Biessen
authors.affiliation: Division of Biopharmaceutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
authors.forename: Johan
authors.initials: J
authors.lastname: Kuiper
authors.affiliation: Division of Biopharmaceutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands; Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Ilze
authors.initials: I
authors.lastname: Bot
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000097:blood; D050197:Atherosclerosis / Q000097:blood*; D018450:Disease Progression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016086:Lentivirus / Q000235:genetics; D008407:Mast Cells / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009478:Neuropeptide Y / Q000097:blood*; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000473:pathology*; D053802:Tryptases / Q000097:blood
chemical_list: D001057:Apolipoproteins E; D015850:Interleukin-6; D009478:Neuropeptide Y; D053802:Tryptases
keywords: Atherosclerosis; Lentivirus; Mast cell; Nerve fiber; Neuropeptide Y