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Snail1 is positively correlated with atrial fibrosis in patients with atrial fibrillation and rheumatic heart disease

机译:Snail1与心房纤颤和风湿性心脏病患者的心房纤维化呈正相关

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摘要

The present study investigated the association between Snail1 and atrial fibrosis in patients with atrial fibrillation (AF) and rheumatic heart disease (RHD) and to determine the possible mechanism underlying this interrelation. A total of 19 patients were included in the current study and were divided into two groups: A sinus rhythm (SR) group (n=9) and an AF group (n=10). All patients underwent heart valve replacement surgery, during which ~200 mg right atrium tissue was obtained. Hematoxylin and eosin and Masson's trichrome-stained sections were used to evaluate the morphological changes of cardiomyocytes and the level of fibrosis. Immunohistochemistry was applied to observe the location and expression of Snail1. Reverse transcription-quantitative polymerase chain reaction was used to measure Snail1 mRNA levels. Western blotting was used to determine changes in the expression of Snail1, as well as in the expression of proteins involved in the Wnt pathway, including Wnt1, Wnt 3a, Wnt8a, Wnt5a and Wnt11. Compared with the SR group, expanded cardiomyocytes and higher collagen deposition was detected in the atrial tissue of the AF group. The expression of Snail1 mRNA and protein was significantly higher in the AF group than in the SR group (P<0.05). Additionally, the expression of Wnt1, 3a and 8a in the canonical Wnt signaling pathway, and Wnt5a and 11 in the noncanonical Wnt signaling pathway were significantly increased in the AF group. Furthermore, the phosphorylation level of glycogen synthase kinase 3β (GSK3β) and the levels of β-catenin and GSK3β were significantly increased in the AF group compared with the SR group (P<0.05). Snail1 may be involved in the development and maintenance of atrial fibrosis in patients with atrial fibrillation and rheumatic heart disease and may be developed as a novel biomarker to evaluate myocardial fibrosis in the future. Additionally, the current study suggests that the Wnt signaling pathway may participate in the process of increased Snail1 expression and atrial fibrosis in patients with AF and RHD.
机译:本研究调查了Snail1与房颤(AF)和风湿性心脏病(RHD)患者的房颤之间的关系,并确定了这种相互关系的可能机制。本研究共纳入19位患者,分为两组:窦性心律(SR)组(n = 9)和AF组(n = 10)。所有患者均接受了心脏瓣膜置换手术,在此期间获得了约200 mg右心房组织。使用苏木精和曙红以及Masson的三色染色切片评估心肌细胞的形态变化和纤维化水平。免疫组织化学法观察Snail1的定位和表达。逆转录-定量聚合酶链反应用于测量Snail1 mRNA水平。 Western印迹用于确定Snail1的表达以及Wnt通路中涉及的蛋白质(包括Wnt1,Wnt 3a,Wnt8a,Wnt5a和Wnt11)表达的变化。与SR组相比,在AF组的心房组织中检测到了扩张的心肌细胞和更高的胶原蛋白沉积。 AF组Snail1 mRNA和蛋白的表达明显高于SR组(P <0.05)。此外,在AF组中,经典Wnt信号通路中Wnt1、3a和8a的表达以及非经典Wnt信号通路中Wnt5a和11的表达均显着增加。此外,与SR组相比,AF组糖原合酶激酶3β(GSK3β)的磷酸化水平以及β-catenin和GSK3β的水平显着升高(P <0.05)。 Snail1可能参与心房颤动和风湿性心脏病患者心房纤维化的发展和维持,并且有可能在将来开发为评估心肌纤维化的新型生物标记物。此外,当前的研究表明Wnt信号通路可能参与AF和RHD患者Snail1表达增加和心房纤维化的过程。

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