Caveolin-1 Deficiency Induces Atrial Fibrosis and Increases Susceptibility to Atrial Fibrillation by the STAT3 Signaling Pathway.
J Cardiovasc Pharmacol
; 78(2): 175-183, 2021 08 01.
Article
em En
| MEDLINE
| ID: mdl-34554674
ABSTRACT
ABSTRACT Atrial fibrillation (AF) is a common arrhythmia in the clinic. Ablation failure and recurrence after cardioversion have become medical problems worldwide. An important pathological feature of AF is atrial fibrosis, which increases susceptibility to AF. As an important target of fibrosis signal integration, the signal transducer and activator of transcription 3 (STAT3) signaling pathway plays an important role in fibrosis. Caveolin-1 (CAV1), a cell membrane protein, is involved in a variety of the biological functions of cells. However, the role of CAV1 in atrial fibrosis remains unclear. In this study, Masson's trichrome staining was used to detect the degree of atrial fibrosis, and the expression of CAV1 in the human atrium was evaluated by immunohistochemistry. To further study the role of CAV1, its expression in cultured rat atrial fibroblasts was silenced using siRNAs. Atrial fibroblasts were treated with angiotensin II to observe the effects on CAV1 and the transforming growth factor-ß1 and STAT3 signaling pathways. We also detected the effects of CAV1 scaffolding domain (CSD) peptide on fibrosis through the addition of exogenous CSD peptide. The results showed that CAV1 expression decreased with the aggravation of atrial fibrosis and that this effect increased the incidence of AF. The depletion of CAV1 induced excessive extracellular matrix deposition by activating the STAT3 and transforming growth factor-ß1/SMAD2 signaling pathways, and this effect was exacerbated by stimulation with angiotensin II and improved by CSD peptide. These data suggested that CAV1 not only plays a critical role in fibrosis progression but also provides a target for the treatment of atrial fibrosis and AF.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fibrilação Atrial
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Caveolina 1
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Fator de Transcrição STAT3
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Fibroblastos
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Remodelamento Atrial
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Átrios do Coração
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Frequência Cardíaca
Limite:
Adult
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Aged
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article