Titre :

Endothelial, but not smooth muscle, peroxisome proliferator-activated receptor β/δ regulates vascular permeability and anaphylaxis.

Auteur(s) :

Wawrzyniak, Marta [Auteur]
Center for Integrative Genomics - Institute of Bioinformatics, Génopode [CIG]
Pich, Christine [Auteur]
Center for Integrative Genomics - Institute of Bioinformatics, Génopode [CIG]
Gross, Barbara [Auteur]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Schütz, Frédéric [Auteur]
Swiss Institute of Bioinformatics [Lausanne] [SIB]
Center for Integrative Genomics - Institute of Bioinformatics, Génopode [CIG]
Fleury, Sébastien [Auteur]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Quemener, Sandrine [Auteur]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Sgandurra, Marie [Auteur]
Center for Integrative Genomics - Institute of Bioinformatics, Génopode [CIG]
Bouchaert, Emmanuel [Auteur]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Moret, Catherine [Auteur]
Center for Integrative Genomics - Institute of Bioinformatics, Génopode [CIG]
Mury, Lionel [Auteur]
Center for Integrative Genomics - Institute of Bioinformatics, Génopode [CIG]
Rommens, Corinne [Auteur]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Mottaz, Hélène [Auteur]
Center for Integrative Genomics - Institute of Bioinformatics, Génopode [CIG]
Dombrowicz, David [Auteur]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Michalik, Liliane [Auteur]
Center for Integrative Genomics - Institute of Bioinformatics, Génopode [CIG]

Titre de la revue :

Journal of Allergy and Clinical Immunology

Pagination :

1625-1635e5

Éditeur :

Elsevier

Date de publication :

2015-06

ISSN :

0091-6749

Mot(s)-clé(s) en anglais :

vascular permeability
Peroxisome proliferator-activated receptor β/δ
anaphylaxis
endothelium
smooth muscle cells

Discipline(s) HAL :

Sciences du Vivant [q-bio]/Immunologie

Résumé en anglais : [en]

Remodeling of quiescent vessels with increases in permeability, vasodilatation, and edema are hallmarks of inflammatory disorders. Factors involved in this type of remodeling represent potential therapeutic targets. We ...
Lire la suite >Remodeling of quiescent vessels with increases in permeability, vasodilatation, and edema are hallmarks of inflammatory disorders. Factors involved in this type of remodeling represent potential therapeutic targets. We investigated whether the nuclear hormone receptor peroxisome proliferator-activated receptor (PPAR) β/δ, a regulator of metabolism, fibrosis, and skin homeostasis, is involved in regulation of this type of remodeling. Wild-type and various Pparb/d mutant mice were used to monitor dermal acute vascular hyperpermeability (AVH) and passive systemic anaphylaxis-induced hypothermia and edema. PPARβ/δ-dependent kinase activation and remodeling of endothelial cell-cell junctions were addressed by using human endothelial cells. AVH and dilatation of dermal microvessels stimulated by vascular endothelial growth factor A, histamine, and thrombin are severely compromised in PPARβ/δ-deficient mice. Selective deletion of the Pparb/d-encoding gene in endothelial cells in vivo similarly limits dermal AVH and vasodilatation, providing evidence that endothelial PPARβ/δ is the major player in regulating acute dermal microvessel remodeling. Furthermore, endothelial PPARβ/δ regulatory functions are not restricted to the skin vasculature because its deletion in the endothelium, but not in smooth muscle cells, also leads to reduced systemic anaphylaxis, the most severe form of allergic reaction, in which an acute vascular response plays a key role. PPARβ/δ-dependent AVH activation likely involves the activation of mitogen-activated protein kinase and Akt pathways and leads to downstream destabilization of endothelial cell-cell junctions. These results unveil not only a novel function of PPARβ/δ as a direct regulator of acute vessel permeability and dilatation but also provide evidence that antagonizing PPARβ/δ represents an important strategy to consider for moderating diseases with altered endothelial integrity, such as acute inflammatory and allergic disorders.Lire moins >

Langue :

Anglais

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Collections :

• Récepteurs nucléaires, Maladies Cardiovasculaires et Diabète (RNMCD) - U1011

Source :

Harvested from HAL