Involvement of plasminogen activator inhibitor-1 and its related molecules in atrial fibrosis in patients with atrial fibrillation.
Involvement of plasminogen activator inhibitor-1 and its related molecules in atrial fibrosis in patients with atrial fibrillation.
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纤溶酶原激活物抑制剂-1及其相关分子在房颤患者心房纤维化中的作用
作者：
Li Q;Lai Y;Gao X;Li X;Deng CY;Guo H;Zhao J;Yang H;Xu Y;Wu S;Xue Y;Rao F
心房颤动是心律失常的最常见形式。心房纤维化是心房颤动的一个显着特征，但其机制尚不清楚。我们检索了 Gene Expression Omnibus 数据库，比较了房颤和窦性心律样本之间的 mRNA 表达模式；鉴定出一百四十八个差异表达基因。这些基因大多数在细胞外基质组织过程和胶原激活酪氨酸激酶受体信号通路中显着富集。为了筛选参与心房纤维化的枢纽基因，我们构建了蛋白质-蛋白质相互作用网络，发现三个枢纽基因（SERPINE1/纤溶酶原激活剂抑制剂-1/PAI-1、TIMP金属肽酶抑制剂3/TIMP3和核心蛋白聚糖/DCN）在心房纤维化中发挥着重要作用，尤其是纤溶酶原激活剂抑制剂-1。纤溶酶原激活物抑制剂-1 表达升高与 p53 信号通路呈正相关。通过蛋白质印迹分析验证窦性心律和心房颤动患者中纤溶酶原激活剂抑制剂-1 和 p53 蛋白表达水平。与窦性心律对照相比，房颤患者心房组织中 p53 和纤溶酶原激活物抑制剂-1 蛋白表达上调。根据细胞和分子实验的结果，p53还被发现可以调节纤溶酶原激活剂抑制剂-1。因此，p53/纤溶酶原激活剂抑制剂-1信号轴可能参与心房颤动的病理生理过程，并且纤溶酶原激活剂抑制剂-1可能作为心房颤动的新的治疗生物标志物。
Atrial fibrillation is the most common form of cardiac arrhythmia. Atrial fibrosis is a significant feature of atrial fibrillation though its mechanism is not well understood. We searched the Gene Expression Omnibus database to compare mRNA expression patterns between atrial fibrillation and sinus rhythm samples; one hundred and forty eight differentially expressed genes were identified. Most of these genes were significantly enriched in the extracellular matrix organization process and collagen-activated tyrosine kinase receptor signaling pathway. To screen hub genes involved in atrial fibrosis, we constructed a protein-protein interaction network and found that three hub genes (SERPINE1/plasminogen activator inhibitor-1/PAI-1, TIMP Metallopeptidase Inhibitor 3/TIMP3 and decorin/DCN) play vital roles in atrial fibrosis, especially plasminogen activator inhibitor-1. Elevated plasminogen activator inhibitor-1 expression was positively correlated with the p53 signaling pathway. Plasminogen activator inhibitor-1 and p53 protein expression levels were verified in patients with sinus rhythm and atrial fibrillation by Western blot analysis. Compared with the sinus rhythm controls, p53 and plasminogen activator inhibitor-1 protein expressions were upregulated in the atrial tissues of patients with atrial fibrillation. p53 was also found to regulate plasminogen activator inhibitor-1 based on the results of cellular and molecular experiments. Thus, the p53/plasminogen activator inhibitor-1 signaling axis may participate in the pathophysiological processes of atrial fibrillation, and plasminogen activator inhibitor-1 may serve as a new therapeutic biomarker in atrial fibrillation.
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影响因子：
1.5
作者：
Cheng, Hai;Chen, Yuhan;Xu, Biao
通讯作者：
Xu, Biao
DOI：
10.1093/bioinformatics/btp101
发表时间：
2009-04-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Bindea G;Mlecnik B;Hackl H;Charoentong P;Tosolini M;Kirilovsky A;Fridman WH;Pagès F;Trajanoski Z;Galon J
通讯作者：
Galon J
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14.9
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作者：
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影响因子：
37.8
作者：
Pretorius, Mias;Donahue, Brian S.;Brown, Nancy J.
通讯作者：
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