Role of angiopoietin-like protein 2 in atrial fibrosis induced by human epicardial adipose tissue: Analysis using an organo-culture system.
Adipose Tissue
/ metabolism
Aged
Aged, 80 and over
Angiopoietin-Like Protein 2
Angiopoietin-like Proteins
/ metabolism
Atrial Fibrillation
/ diagnosis
Female
Fibroblasts
/ metabolism
Fibrosis
/ metabolism
Heart Atria
/ metabolism
Humans
Male
Middle Aged
Myocardium
/ metabolism
Organ Culture Techniques
Pericardium
/ metabolism
Angptl2
Atrial fibrillation
Atrial myocardial fibrosis
Epicardial adipose tissue
Inflammation
Subcutaneous adipose tissue
Journal
Heart rhythm
ISSN: 1556-3871
Titre abrégé: Heart Rhythm
Pays: United States
ID NLM: 101200317
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
18
10
2019
revised:
02
04
2020
accepted:
12
04
2020
pubmed:
25
4
2020
medline:
7
9
2021
entrez:
25
4
2020
Statut:
ppublish
Résumé
We have recently reported that peri-left atrial epicardial adipose tissue (EAT) is associated with atrial myocardial fibrosis, in which angiopoietin-like protein 2 (Angptl2) protein content in EAT is associated with atrial myocardial fibrosis. This study aimed to examine whether Angptl2 contained in peri-left atrial EAT can induce atrial myocardial fibrosis. Human peri-left atrial EAT and abdominal subcutaneous adipose tissue (SAT) were collected from 9 autopsy cases. EAT- or SAT-conditioned medium was dropped onto the rat left atrial epicardial surface using an organo-culture system. Conditioned medium, recombinant Angptl2, and its antibody effects on organo-cultured rat atrial myocardial fibrosis were evaluated. Angptl2 effects on cultured neonatal rat fibroblasts were also investigated. EAT-conditioned medium induced atrial fibrosis in organo-cultured rat atrium with a progressive increase in the number of myofibroblasts. The profibrotic effect of EAT was greater than that of SAT. EAT in patients with atrial fibrillation induced a more significant atrial fibrosis than in those without. Treatment with human recombinant Angptl2 induced fibrosis in organo-cultured rat atrium, which was suppressed by the concomitant treatment with Angptl2 antibody. In cultured fibroblasts, Angptl2 upregulated the expression of α-smooth muscle actin, transforming growth factor-β1, phospho-extracellular signal-regulated kinase,phospho-inhibitor of κBα, and phospho-p38 mitogen-activated protein kinase. This study demonstrated that Angptl2 contained in EAT played a crucial role in EAT-induced inflammatory atrial fibrosis. The results also suggested that antagonizing the expression of Angptl2 in EAT can be a novel therapeutic approach to prevent atrial fibrillation.
Sections du résumé
BACKGROUND
We have recently reported that peri-left atrial epicardial adipose tissue (EAT) is associated with atrial myocardial fibrosis, in which angiopoietin-like protein 2 (Angptl2) protein content in EAT is associated with atrial myocardial fibrosis.
OBJECTIVE
This study aimed to examine whether Angptl2 contained in peri-left atrial EAT can induce atrial myocardial fibrosis.
METHODS
Human peri-left atrial EAT and abdominal subcutaneous adipose tissue (SAT) were collected from 9 autopsy cases. EAT- or SAT-conditioned medium was dropped onto the rat left atrial epicardial surface using an organo-culture system. Conditioned medium, recombinant Angptl2, and its antibody effects on organo-cultured rat atrial myocardial fibrosis were evaluated. Angptl2 effects on cultured neonatal rat fibroblasts were also investigated.
RESULTS
EAT-conditioned medium induced atrial fibrosis in organo-cultured rat atrium with a progressive increase in the number of myofibroblasts. The profibrotic effect of EAT was greater than that of SAT. EAT in patients with atrial fibrillation induced a more significant atrial fibrosis than in those without. Treatment with human recombinant Angptl2 induced fibrosis in organo-cultured rat atrium, which was suppressed by the concomitant treatment with Angptl2 antibody. In cultured fibroblasts, Angptl2 upregulated the expression of α-smooth muscle actin, transforming growth factor-β1, phospho-extracellular signal-regulated kinase,phospho-inhibitor of κBα, and phospho-p38 mitogen-activated protein kinase.
CONCLUSION
This study demonstrated that Angptl2 contained in EAT played a crucial role in EAT-induced inflammatory atrial fibrosis. The results also suggested that antagonizing the expression of Angptl2 in EAT can be a novel therapeutic approach to prevent atrial fibrillation.
Identifiants
pubmed: 32330625
pii: S1547-5271(20)30359-3
doi: 10.1016/j.hrthm.2020.04.027
pii:
doi:
Substances chimiques
ANGPTL2 protein, human
0
Angiopoietin-Like Protein 2
0
Angiopoietin-like Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1591-1601Informations de copyright
Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.