Decreased M1 macrophage polarization in dabigatran-treated Ldlr-deficient mice: Implications for atherosclerosis and adipose tissue inflammation.
Adipose Tissue
/ drug effects
Animals
Antithrombins
/ pharmacology
Aorta, Thoracic
/ drug effects
Atherosclerosis
/ drug therapy
Dabigatran
/ pharmacology
Disease Models, Animal
Female
Flow Cytometry
Immunohistochemistry
Inflammation
/ drug therapy
Macrophage Activation
/ physiology
Macrophages
/ metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Atherosclerosis
Inflammation
Macrophage
Obesity
Thrombin inhibitor
Journal
Atherosclerosis
ISSN: 1879-1484
Titre abrégé: Atherosclerosis
Pays: Ireland
ID NLM: 0242543
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
06
06
2018
revised:
14
05
2019
accepted:
07
06
2019
pubmed:
25
6
2019
medline:
9
7
2020
entrez:
25
6
2019
Statut:
ppublish
Résumé
The non-vitamin K oral anticoagulant dabigatran etexilate (dabigatran) is increasingly prescribed to patients with non-valvular atrial fibrillation and venous thromboembolism. Adipose tissue (AT) inflammation during obesity plays a crucial role in the development of insulin resistance, type II diabetes and atherogenesis. The aim of the present study was to investigate the effects of thrombin inhibition by dabigatran in a combined model of diet-induced obesity and atherosclerosis. Female Low density lipoprotein receptor knockout (Lldr Dabigatran-treated animals showed increased adipocyte hypertrophy, but reduced numbers of pro-inflammatory M1-polarized macrophages in the adipose tissue. Abundance of pro-inflammatory M1 macrophages was also decreased in the aortic wall of dabigatran-fed mice. Multiple circulating cytokines were reduced, indicating an effect in systemically relevant secretory compartments such as the AT. Dabigatran treatment reduces pro-inflammatory M1 macrophages in atherosclerotic lesions, thereby contributing to plaque stabilizing and atheroprotective effects of the thrombin inhibitor. This finding is not restricted to the vascular wall but is also present in AT where dabigatran treatment reduced the release of pro-inflammatory cytokines and accumulation of M1 macrophages.
Sections du résumé
BACKGROUND AND AIMS
The non-vitamin K oral anticoagulant dabigatran etexilate (dabigatran) is increasingly prescribed to patients with non-valvular atrial fibrillation and venous thromboembolism. Adipose tissue (AT) inflammation during obesity plays a crucial role in the development of insulin resistance, type II diabetes and atherogenesis. The aim of the present study was to investigate the effects of thrombin inhibition by dabigatran in a combined model of diet-induced obesity and atherosclerosis.
METHODS
Female Low density lipoprotein receptor knockout (Lldr
RESULTS
Dabigatran-treated animals showed increased adipocyte hypertrophy, but reduced numbers of pro-inflammatory M1-polarized macrophages in the adipose tissue. Abundance of pro-inflammatory M1 macrophages was also decreased in the aortic wall of dabigatran-fed mice. Multiple circulating cytokines were reduced, indicating an effect in systemically relevant secretory compartments such as the AT.
CONCLUSIONS
Dabigatran treatment reduces pro-inflammatory M1 macrophages in atherosclerotic lesions, thereby contributing to plaque stabilizing and atheroprotective effects of the thrombin inhibitor. This finding is not restricted to the vascular wall but is also present in AT where dabigatran treatment reduced the release of pro-inflammatory cytokines and accumulation of M1 macrophages.
Identifiants
pubmed: 31233979
pii: S0021-9150(19)31354-1
doi: 10.1016/j.atherosclerosis.2019.06.897
pii:
doi:
Substances chimiques
Antithrombins
0
Dabigatran
I0VM4M70GC
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
81-88Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.