Key result
Activation of IGF-1R facilitated myocardial fibrosis and expedited the occurrence of atrial fibrillation through the PI3K/Akt/FoxO3a signaling pathway in rat and human fibroblast models.
Why the study?
Atrial structural remodeling is critical to AF occurrence and maintenance, and IGF-1R plays a role in tissue fibrosis, but its mechanism in atrial remodeling remained unclear.
Activation of IGF-1R promotes atrial structural remodeling and myocardial fibrosis via the PI3K/Akt/FoxO3a pathway, contributing to the maintenance of atrial fibrillation.
Answers are grounded in this paper and cite their sources.
Hypothesis-generating for IGF-1R targeting in AF; requires clinical validation before any practice implications.
Atrial structural remodeling takes on a critical significance to the occurrence and maintenance of atrial fibrillation (AF). As revealed by recent data, insulin-like growth factor-1 receptor (IGF-1R) plays a certain role in tissue fibrosis. In this study, the mechanism of IGF-1R in atrial structural remodeling was examined based on in vivo and in vitro experiments. First, cluster analysis of AF hub genes was conducted, and then the molecular mechanism was proposed by which IGF-1R regulates myocardial fibrosis via the PI3K/Akt/FoxO3a pathway. Subsequently, the mentioned mechanism was verified in human cardiac fibroblasts (HCFs) and rats transduced with IGF-1 overexpression type 9 adeno-associated viruses. The results indicated that IGF-1R activation up-regulated collagen Ⅰ protein expression and Akt phosphorylation in HCFs and rat atrium. The administration of LY294002 reversed the above phenomenon, improved the shortening of atrial effective refractory period, and reduced the increased incidence of AF and atrial fibrosis in rats. The transfection of FoxO3a siRNA reduced the anti-fibrotic effect of LY294002 in HCFs. The above data revealed that activation of IGF-1R takes on a vital significance to atrial structural remodeling by facilitating myocardial fibrosis and expediting the occurrence and maintenance of AF through the regulation of the PI3K/Akt/FoxO3a signaling pathway.
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Zhang et al. (2023) studied Atrial fibrillation. IGF-1R activation was evaluated on Myocardial fibrosis and incidence of atrial fibrillation. Activation of IGF-1R facilitated myocardial fibrosis and expedited the occurrence of atrial fibrillation through the PI3K/Akt/FoxO3a signaling pathway in rat and human fibroblast models.
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