[Relationship between FGF23/FGFR4 expression in atrial tissue and atrial fibrosis in patients with atrial fibrillation]

Zhonghua Yi Xue Za Zhi. 2018 Apr 3;98(13):1003-1007. doi: 10.3760/cma.j.issn.0376-2491.2018.13.010.
[Article in Chinese]

Abstract

Objective: To observe the expression of fibroblast growth factor 23 (FGF23) and FGFR4 in patients with atrial fibrillation (AF) and its relationship with atrial fibrosis. Methods: Fifty-one patients with rheumatic heart disease undergoing cardiac surgery at the Second Affiliated Hospital of Nanchang University from October 2016 to April 2017 were divided into two groups according to whether they were complicated with atrial fibrillation: 39 patients with persistent AF(AF group), and 12 patients with sinus rhythm (SR group). The right atrial appendage was cut out during cardiac surgery. The expression of FGF23 and FGFR4 mRNA was detected by quantitative real-time PCR. The expression of FGFR4 protein was detected by Western blot. Atrial structure was evaluated by echocardiography. Masson staining was used to evaluate the degree of atrial fibrosis. The expression of FGF23 and FGFR4 was compared between the two groups.Additionally, the relationship between FGF23 and FGFR4 expression and atrial fibrosis was evaluated. Results: AF group had significantly higher right and left atrial diameter than SR group((40.1±1.6 )mm vs (34.1±1.5)mm, (52.4±2.9)mm vs (41.3±2.4)mm, all P<0.05) . There were no statistically significant differences in age, gender, ejection fraction between the two groups. The expression of FGF23 and FGFR4 mRNA in AF group were significantly higher than those in SR group (1.93±0.32 vs 0.93±0.14, 1.89±0.17 vs 0.91±0.11, both P<0.05). Compared with the SR group, the protein expression of FGFR4 in the AF group was significantly higher(1.76±0.21 vs 0.84±0.12). In AF group, there was no correlation between FGF23 mRNA and atrial diameter (r=0.274 (left atrial), r=0.238 (right atrium), both P>0.05). Meanwhile, FGFR4 mRNA and protein expression had no correlation with atrial diameter either. There was positive correlation between FGF23 mRNA and atrial collagen volume fraction in AF group (r=0.42, P<0.05). The expression of FGFR4 mRNA and protein were positively correlated with the atrial collagen volume fraction (r=0.573, r=0.478, all P<0.05). Conclusion: The expression of FGF23 and FGFR4 in atrial fibrillation patients is increased, which is positively correlated with atrial fibrosis, suggesting that FGF23/FGFR4 pathway may play an important role in atrial fibrillation by promoting atrial fibrosis.

目的: 观察心房颤动患者心房组织成纤维细胞生长因子23(FGF23)和FGFR4的表达及其与心房纤维化的关系。 方法: 选择2016年10月至2017年4月在南昌大学第二附属医院心脏外科行心脏手术的风湿性心脏病患者51例,按照是否合并房颤分为两组:持续性房颤组39例(AF组),窦性心律组12例(SR组),于心脏手术时切取小块右心耳组织,采用实时荧光定量PCR法检测FGF23、FGFR4 mRNA的表达量,采用Western印迹检测FGFR4蛋白表达量,行心脏超声评价心房结构情况,采用Masson染色评价心房纤维化程度,比较两组患者FGF23、FGFR4表达及评价FGF23、FGFR4表达与心房纤维化的关系。 结果: 两组患者心脏超声结果及年龄、性别的比较,AF组患者右心房与左心房内径均大于SR组[(40.1±1.6)mm比(34.1±1.5)mm,(52.4±2.9)mm比(41.3±2.4)mm,均P<0.05]。两组间其他各项指标如年龄、性别、射血分数等差异无统计学意义。AF组患者FGF23和FGFR4 mRNA表达量高于SR组(1.93±0.32比0.93±0.14,1.89±0.17比0.91±0.11)(均P<0.05),AF组FGFR4蛋白表达量高于SR组(1.76±0.21比0.84±0.12)。AF组FGF23 mRNA与心房内径无相关性[r=0.274 (左房),r=0.238 (右房),均P>0.05], FGFR4 mRNA和蛋白表达量同样与心房内径无相关性。AF组FGF23 mRNA与心房胶原容积分数呈正相关(r=0.42,P<0.05), FGFR4 mRNA及蛋白表达量与心房胶原容积分数均呈正相关(r=0.573,r=0.478,均P<0.05)。 结论: 房颤患者心房组织FGF23和FGFR4表达均增加,与心房纤维化呈正相关,提示FGF23/FGFR4通路可通过促进心房纤维化在房颤中起作用。.

Keywords: Atrial fibrillation; Atrial fibrosis; Fibroblast growth factor 23; Fibroblast growth factor receptor 4; Rheumatic heart disease.

MeSH terms

  • Atrial Appendage
  • Atrial Fibrillation*
  • Fibroblast Growth Factor-23
  • Heart Atria
  • Humans
  • Receptor, Fibroblast Growth Factor, Type 4
  • Rheumatic Heart Disease

Substances

  • FGF23 protein, human
  • Fibroblast Growth Factor-23
  • FGFR4 protein, human
  • Receptor, Fibroblast Growth Factor, Type 4