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

Details

Serval ID
serval:BIB_1ED6EDEE8520
Type
Article: article from journal or magazin.
Collection
Publications
Title
Endothelial, but not smooth muscle, peroxisome proliferator-activated receptor β/δ regulates vascular permeability and anaphylaxis.
Journal
Journal of Allergy and Clinical Immunology
Author(s)
Wawrzyniak M., Pich C., Gross B., Schütz F., Fleury S., Quemener S., Sgandurra M., Bouchaert E., Moret C., Mury L., Rommens C., Mottaz H., Dombrowicz D., Michalik L.
ISSN
1097-6825 (Electronic)
ISSN-L
0091-6749
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
135
Number
6
Pages
1625-1635.e5
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
BACKGROUND: 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.
OBJECTIVES: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.
Keywords
Peroxisome proliferator-activated receptor beta/delta, anaphylaxis, vascular permeability, endothelium, smooth muscle cells
Pubmed
Web of science
Create date
22/12/2014 9:53
Last modification date
20/08/2019 13:54
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