Provincial Clinical Medicine College of Fujian Medical University, Fuzhou, PR China.
Department of Cardiology, Fujian Provincial Hospital, Fuzhou, PR China.
J Cell Mol Med. 2019 Apr;23(4):3032-3039. doi: 10.1111/jcmm.14165. Epub 2019 Jan 29.
This study aimed to investigate the effects of transforming growth factor β1 (TGF β1) and hepatocyte growth factor (HGF) on the expression of connective tissue growth factor (CTGF) in human atrial fibroblasts, and to explore the relationship of these factors in atrial fibrosis and atrial anatomical remodelling (AAR) of patients with atrial fibrillation (AF).
Fresh right auricular appendix tissue of 20 patients with rheumatic heart disease undergoing valve replacement surgery was collected during surgeries, 10 patients had sinus rhythm(SR), and 10 patients had chronic atrial fibrillation (CAF). Atrial fibroblasts were then cultured from the tissues with differential attachment technique and treated with either TGFβ1 (10 ng/mL) or HGF (100 ng/mL). CTGF mRNA levels were measured by RT-PCR, and CTGF protein content was determined using immunofluorescence and Western blotting assays.
CAF group had higher left atrial diameters (LADs) and higher CTGF mRNA expression in atrial fibroblasts compared with SR group. The CTGF protein content in CAF group was higher than that of SR group and positively correlated with LAD and AF duration. After CAF group was treated with TGFβ1, CTGF mRNA and protein expression were significantly down-regulated, whereas when treated with HGF, expression was up-regulated compared with SR group.
Increased CTGF expression was associated with enlarged LAD, atrial fibrosis and AAR in patients with AF. TGFβ1 and HGF regulate CTGF expression in human atrial fibroblasts with up-regulation of mRNA and down-regulation of protein, therefore, either promote or inhibit atrial fibrosis, which could be related to the incidence and persistence of AF.
本研究旨在探讨转化生长因子β1（TGFβ1）和肝细胞生长因子（HGF）对人心房成纤维细胞结缔组织生长因子（CTGF）表达的影响，并探讨这些因子与心房颤动（AF）患者心房纤维化和心房解剖重构（AAR）的关系。
术中采集 20 例风湿性心脏病行瓣膜置换术患者右心耳组织，其中窦性心律（SR）10 例，慢性心房颤动（CAF）10 例。采用差速贴壁法从组织中培养心房成纤维细胞，分别用 TGFβ1（10ng/ml）或 HGF（100ng/ml）处理。采用 RT-PCR 检测 CTGF mRNA 水平，免疫荧光和 Western blot 检测 CTGF 蛋白含量。
与 SR 组相比，CAF 组左心房直径（LAD）较大，心房成纤维细胞 CTGF mRNA 表达较高。CAF 组 CTGF 蛋白含量高于 SR 组，与 LAD 和 AF 持续时间呈正相关。CAF 组经 TGFβ1 处理后，CTGF mRNA 和蛋白表达明显下调，而经 HGF 处理后，表达上调，与 SR 组相比。
CTGF 表达增加与 AF 患者的 LAD 增大、心房纤维化和 AAR 有关。TGFβ1 和 HGF 调节人心房成纤维细胞 CTGF 的表达，上调 mRNA 而下调蛋白，因此，可促进或抑制心房纤维化，这可能与 AF 的发生和持续有关。
