Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taiwan.
Circ J. 2011;75(7):1592-600. doi: 10.1253/circj.cj-10-0892. Epub 2011 May 17.
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.
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.
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.
心房纤维化是心房颤动（AF）结构重构的特征。结缔组织生长因子（CTGF）是一种有效的促纤维化因子，但 CTGF 在 AF 中的作用尚未完全阐明。
从 20 例行心脏手术的患者（窦性心律 10 例，AF 10 例）中获得右心耳。AF 患者的 CTGF mRNA 水平、蛋白水平和免疫组织化学染色均显著增加。在猪 AF 模型中，心房组织血管紧张素 II（Ang II）和 CTGF 水平在两个心房均显著上调。在灌注的大鼠心脏中，Ang II 刺激增加了 CTGF 的表达，而 Ang II 型 1 受体拮抗剂可以抑制其表达。在细胞培养系统中，Ang II 处理下心房成纤维细胞和心肌细胞均能增加 CTGF 的表达。Ang II 型 1 受体拮抗剂可抑制 Ang II 诱导的 CTGF 表达。用重组 CTGF 处理后，心房成纤维细胞表达胶原 I 的水平增加。此外，CTGF 水平与 AF 猪的组织 Ang II 含量高度相关。
AF 患者和动物表现出 CTGF 表达显著增加。Ang II 刺激可上调心房成纤维细胞和心肌细胞中 CTGF 的表达。Ang II 诱导的 CTGF 表达可能参与了心房基质重构。
