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题目:: Rac1-Induced Connective Tissue Growth Factor regulates Connexin 43 and N-Cadherin Expression in Atrial Fibrillation
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状态:: 发布时间Feb. 21, 2010 , 更新时间 May 4, 2014 , 提交时间 Feb. 24, 2009,
物种:: Homo sapiens
摘要:: Objectives: We studied the signal transduction of atrial structural remodelling that contributes to the pathogenesis of atrial fibrillation (AF). Backround: Fibrosis is a hallmark of arrhythmogenic structural remodelling but the underlying molecular mechanisms are incompletely understood. Methods: We performed transcriptional profiling of left atrial myocardium (LA) from patients with AF and sinus rhythm (SR) and applied cultured primary cardiac cells and transgenic mice with overexpression of constitutively active V12Rac1 (RacET) who develop AF at old age to characterize mediators of the signal transduction of atrial remodeling. Results: LA from patients with AF showed a marked upregulation of connective tissue growth factor (CTGF) expression compared SR patients. This was associated with increased fibrosis, NADPH-oxidase-, Rac1- and RhoA activity, upregulation of N-cadherin and connexin 43 (Cx43) expression and increased angiotensin II tissue concentration. In neonatal rat cardiac myocytes and -fibroblasts, a specific small molecule inhibitor of Rac1 or simvastatin completely prevented the angiotensin II induced upregulation of CTGF, Cx43 and N-cadherin expression. Transfection with small-inhibiting CTGF RNA blocked Cx43 and N-cadherin expression. RacET mice showed upregulation of CTGF, Cx43 and N-cadherin protein expression. Inhibition of Rac1 by oral statin treatment prevented these effects, identifying Rac1 as a key regulator of CTGF in vivo. Conclusion: The data identify CTGF as an important mediator of atrial structural remodelling during AF. Angiotensin II activates CTGF via activation of Rac1 and NADPH oxidase, leading to upregulation of Cx43, N-cadherin and interstitial fibrosis and therefore contributing to the signal transduction of atrial structural remodelling. Array design study consists of 5 Atrial Fibrillation patients and matched 5 samples of patients in sinus rhythm (controls).
实验种类:: transcription profiling by array
样本量:: 10
实验设计:
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数据号:: E-GEOD-14975, GSE14975
数据状态:: 无法自动分析，您可以尝试手动分析数据。

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