Elevated Expression of Connective Tissue Growth Factor in Human Atrial Fibrillation and Angiotensin II-Treated Cardiomyocytes
Elevated Expression of Connective Tissue Growth Factor in Human Atrial Fibrillation and Angiotensin II-Treated Cardiomyocytes
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DOI：
10.1253/circj.cj-10-0892
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发表时间：
2011-07-01
影响因子：
3.3
通讯作者：
Lai, Ling-Ping
中科院分区：
文献类型：
--
作者：
Ko, Wen-Chin;Hong, Chuang-Ye;Lai, Ling-Ping
背景：心房纤维化是心房颤动（AF）结构重塑的一个特征。结缔组织生长因子（CTGF）是一种有效的促纤维化因子，但其在房颤中的作用尚未完全阐明。 方法与结果：取20例接受心脏手术的患者（10例窦性心律，10例房颤）右心耳。 AF患者中CTGF的mRNA水平、蛋白水平和免疫组化染色均显着升高。在猪 AF 模型中，两个心房的组织血管紧张素 II (Ang II) 和 CTGF 水平均显着上调。在灌注大鼠心脏中，Ang II 刺激增加了 CTGF 表达，而 CTGF 表达可被 Ang II I 型受体拮抗剂抑制。在细胞培养系统中，心房成纤维细胞和肌细胞均导致 Ang II 治疗下 CTGF 表达增加。 Ang II I型受体拮抗剂可以抑制Ang II诱导的CTGF表达。重组CTGF治疗后，心房成纤维细胞中胶原蛋白I的表达水平升高。此外，AF猪中CTGF水平与组织Ang II含量高度相关。结论：AF患者和动物的CTGF表达显着升高。 Ang II 刺激上调心房成纤维细胞和肌细胞中 CTGF 的表达。 Ang II 诱导的 CTGF 表达可能参与心房基质重塑。 （Circ J 2011；75：1592-1600）
Background: Atrial fibrosis is a feature of structural remodeling in atrial fibrillation (AF). Connective tissue growth factor (CTGF) is a potent profibrotic factor, but its role of CTGF in AF is not yet fully understood.Methods and Results: Right atrial appendages were obtained from 20 patients who underwent cardiac surgery (10 with sinus rhythm, 10 with AF). The mRNA level, protein level and immunohistochemical staining of CTGF were significantly increased in AF patients. In a porcine AF model, tissue angiotensin II (Ang II) and CTGF levels were significantly upregulated in both atria. In perfused rat hearts, Ang II stimulation increased CTGF expression, which could be inhibited by Ang II type I receptor antagonist. In a cell culture system, both atrial fibroblasts and myocytes were responsible for the increased CTGF expression under Ang II treatment. Ang II type I receptor antagonist could inhibit the Ang II-induced CTGF expression. Treating with recombinant CTGF, atrial fibroblasts expressed an increased level of collagen I. Furthermore, the CTGF level was highly correlated with tissue Ang II content in AF pigs.Conclusions: AF patients and animals exhibited a significantly increased expression of CTGF. Ang II stimulation upregulated CTGF expression in both atrial fibroblasts and myocytes. Ang II-induced CTGF expression might be involved in atrial substrate remodeling. (Circ J 2011; 75: 1592-1600)