Cysteinyl leukotriene signaling through perinuclear CysLT(1) receptors on vascular smooth muscle cells transduces nuclear calcium signaling and alterations of gene expression.

Abstract : Leukotrienes are pro-inflammatory mediators that are locally produced in coronary atherosclerotic plaques. The response induced by cysteinyl leukotrienes (CysLT) in human coronary arteries may be altered under pathological conditions, such as atherosclerosis. The aim of the present study was to elucidate cysteinyl leukotriene signaling in vascular smooth muscle cells (SMCs) and the effects of inflammation on this process. Immunohistochemical analysis of human carotid endarterectomy samples revealed that the CysLT(1) leukotriene receptor was expressed in areas that also stained positive for α-smooth muscle actin. In human coronary artery smooth muscle cells, lipopolysaccharide significantly upregulated the CysLT(1) receptor and significantly enhanced the changes in intracellular calcium induced by leukotriene C(4) (LTC(4)). In these cells, the CysLT(1) receptor exhibited a perinuclear expression, and LTC(4) stimulation predominantly enhanced nuclear calcium increase, which was significantly inhibited by the CysLT(1) receptor antagonist MK-571. Microarray analysis revealed, among a number of significantly upregulated genes after 24 h stimulation of human coronary artery smooth muscle cells with LTC(4), a 5-fold increase in mRNA levels for plasminogen activator inhibitor (PAI)-2. The LTC(4)-induced increase in PAI-2 expression was confirmed by real-time quantitative PCR and ELISA and was inhibited by the CysLT(1) receptor antagonist MK-571 and by calcium chelators. In summary, pro-inflammatory stimulation of vascular SMCs upregulated a perinuclear CysLT(1) receptor expression coupled to nuclear calcium signaling and changes in gene expression, such as upregulation of PAI-2. Taken together, these findings suggest a role of nuclear CysLT(1) receptor signaling in vascular SMCs inducing gene expression patterns associated with atherosclerosis.
Type de document :
Article dans une revue
J Mol Med (Berl), 2012, epub ahead of print. 〈10.1007/s00109-012-0904-1〉
Liste complète des métadonnées

Littérature citée [33 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-00698628
Contributeur : Magnus Back <>
Soumis le : jeudi 17 mai 2012 - 13:42:33
Dernière modification le : jeudi 11 janvier 2018 - 06:27:49
Document(s) archivé(s) le : vendredi 30 novembre 2012 - 11:55:57

Fichier

Eaton2012.pdf
Fichiers éditeurs autorisés sur une archive ouverte

Identifiants

Collections

Citation

Alison Eaton, Edit Nagy, Mathilde Pacault, Jérémy Fauconnier, Magnus Bäck. Cysteinyl leukotriene signaling through perinuclear CysLT(1) receptors on vascular smooth muscle cells transduces nuclear calcium signaling and alterations of gene expression.. J Mol Med (Berl), 2012, epub ahead of print. 〈10.1007/s00109-012-0904-1〉. 〈inserm-00698628〉

Partager

Métriques

Consultations de la notice

125

Téléchargements de fichiers

288