Ikk2-mediated inflammatory activation of arterial endothelial cells promotes the development and progression of atherosclerosis.
Atherosclerosis
Endothelial cells
Ikk-beta
Ikk2
Inflammation
NF-κB
Journal
Atherosclerosis
ISSN: 1879-1484
Titre abrégé: Atherosclerosis
Pays: Ireland
ID NLM: 0242543
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
28
08
2019
revised:
14
05
2020
accepted:
05
06
2020
pubmed:
28
7
2020
medline:
24
6
2021
entrez:
26
7
2020
Statut:
ppublish
Résumé
Inflammatory activation of endothelial cells is considered to be the first step in the development of atherosclerosis. Here, we determined the consequences of chronic endothelial activation via the NF-κB activator Ikk2 (Inhibitor of nuclear factor kappa-B kinase 2, Ikk-beta) on the development and progression of atherosclerosis. We established a conditional transgenic mouse model, expressing a tamoxifen-inducible, constitutively active form of Ikk2 exclusively in arterial endothelial cells (caIkk2 En face preparations of isolated aortas revealed a significant increase in plaque area in caIkk2 Our results show for the first time that chronic inflammatory activation of arterial endothelial cells accelerates the development and progression of atherosclerosis both at early and late stages of disease development. Thus, pharmacological targeting of endothelial inflammation emerges as a promising treatment approach.
Sections du résumé
BACKGROUND AND AIMS
Inflammatory activation of endothelial cells is considered to be the first step in the development of atherosclerosis. Here, we determined the consequences of chronic endothelial activation via the NF-κB activator Ikk2 (Inhibitor of nuclear factor kappa-B kinase 2, Ikk-beta) on the development and progression of atherosclerosis.
METHODS
We established a conditional transgenic mouse model, expressing a tamoxifen-inducible, constitutively active form of Ikk2 exclusively in arterial endothelial cells (caIkk2
RESULTS
En face preparations of isolated aortas revealed a significant increase in plaque area in caIkk2
CONCLUSIONS
Our results show for the first time that chronic inflammatory activation of arterial endothelial cells accelerates the development and progression of atherosclerosis both at early and late stages of disease development. Thus, pharmacological targeting of endothelial inflammation emerges as a promising treatment approach.
Identifiants
pubmed: 32711212
pii: S0021-9150(20)30301-4
doi: 10.1016/j.atherosclerosis.2020.06.005
pii:
doi:
Substances chimiques
NF-kappa B
0
I-kappa B Kinase
EC 2.7.11.10
Ikbkb protein, mouse
EC 2.7.11.10
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
21-31Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.