Vascular neuropeptide Y contributes to atherosclerotic plaque progression and perivascular mast cell activation

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 ather...

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Veröffentlicht in:Atherosclerosis Jg. 235; H. 1; S. 196 - 203
Hauptverfasser: Lagraauw, H. Maxime, Westra, Marijke M., Bot, Martine, Wezel, Anouk, van Santbrink, Peter J., Pasterkamp, Gerard, Biessen, Erik A.L., Kuiper, Johan, Bot, Ilze
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Ireland Elsevier Ireland Ltd 01.07.2014
Schlagworte:
Animals
Apolipoproteins E - blood
Atherosclerosis
Atherosclerosis - blood
Cardiovascular
Disease Progression
Gene Expression Profiling
Gene Expression Regulation
HEK293 Cells
Humans
Immunohistochemistry
Inflammation - blood
Interleukin-6 - blood
Lentivirus
Lentivirus - genetics
Mast cell
Mast Cells - cytology
Mice
Mice, Knockout
Muscle, Smooth, Vascular - metabolism
Nerve fiber
Neuropeptide Y
Neuropeptide Y - blood
Plaque, Atherosclerotic - blood
Plaque, Atherosclerotic - pathology
Tryptases - blood
Neuropeptide Y
Mast cell
Nerve fiber
Lentivirus
Atherosclerosis
ISSN:0021-9150, 1879-1484, 1879-1484
Online-Zugang:Volltext
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Zusammenfassung: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. 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. 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. •Neuropeptide Y is increased in advanced and unstable atherosclerotic lesions.•Local NPY overexpression in apoE−/− mice increased lesion progression.•NPY overexpression resulted in increased perivascular mast cell degranulation.•Stimulation of mast cells with NPY resulted in pro-inflammatory mediator release.•NPY-induced mast cell activation may contribute to the pro-atherogenic effect of NPY.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0021-9150
1879-1484
1879-1484
DOI:10.1016/j.atherosclerosis.2014.04.025