Title :

Disrupting LXRα phosphorylation promotes FoxM1 expression and modulates atherosclerosis by inducing macrophage proliferation

Author(s) :

Gage, M. [Auteur]
Bécares, N. [Auteur]
Louie, R. [Auteur]
Waddington, K. [Auteur]
Zhang, Y. [Auteur]
University of Manchester [Manchester]
Tittanegro, T. [Auteur]
Rodríguez-Lorenzo, S. [Auteur]
Jathanna, A. [Auteur]
Pourcet, B. [Auteur]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U 1011 [RNMCD]
Pello, O. [Auteur]
de la Rosa, J. [Auteur]
Castrillo, A. [Auteur]
Università degli studi della Campania "Luigi Vanvitelli" = University of the Study of Campania Luigi Vanvitelli
Pineda-Torra, I. [Auteur]

Journal title :

Proceedings of the National Academy of Sciences of the United States of America

Publisher :

National Academy of Sciences

Publication date :

2018-06-27

ISSN :

0027-8424

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Significance To date, the importance of liver X receptors (LXRs) in atherosclerosis development has been gleaned from their pharmacological or genetic manipulation. Here, we show that altering LXRα phosphorylation can shape ...
Show more >Significance To date, the importance of liver X receptors (LXRs) in atherosclerosis development has been gleaned from their pharmacological or genetic manipulation. Here, we show that altering LXRα phosphorylation can shape proatherogenic responses to fat-rich diets, uncovering previously unrecognized mechanisms. Disrupting LXRα phosphorylation in myeloid cells triggers global changes in gene expression in macrophages, including the up-regulation of proliferation-promoting factors, consistent with increased proliferation of lesion-resident cells. This leads to an enhanced atherosclerotic plaque burden and plaques with altered phenotypic features. Notably, novel LXRα-regulated targets revealed by impaired LXRα phosphorylation are markedly distinct from those promoted by LXR ligand activation. Overall, this work reveals LXRα phosphorylation as an important determinant of atherosclerosis development. This could be exploited for the design of novel antiatherosclerotic strategies.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

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

Source :

Harvested from HAL