Elevated β1-Adrenergic Receptor Autoantibody Levels Increase Atrial Fibrillation Susceptibility by Promoting Atrial Fibrosis
Elevated β1-Adrenergic Receptor Autoantibody Levels Increase Atrial Fibrillation Susceptibility by Promoting Atrial Fibrosis
复制标题
β1-肾上腺素能受体自身抗体水平升高可促进心房纤维化，从而增加心房颤动的易感性
DOI：
10.3389/fphys.2020.00076
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发表时间：
2020-02-12
影响因子：
4
通讯作者：
Tang, Baopeng
中科院分区：
文献类型：
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作者：
Shang, Luxiang;Zhang, Ling;Tang, Baopeng
目的β 1肾上腺素能受体自身抗体（β 1ARAbs）是心房颤动（AF）的一种致病因子，但其发病机制尚不清楚。我们评估了β 1ARAb水平升高通过促进心房纤维化增加房颤易感性的假设。方法连续入选70例阵发性房颤患者。通过ELISA分析β 1ARAb和循环纤维化生物标志物的血清水平。使用线性回归来检查β 1ARAb水平与左心房直径（LAD）和循环纤维化生物标志物水平的相关性。此外，我们建立了兔β 1ARAb过表达模型。我们进行了电生理研究和多电极阵列记录，以评估心房有效不应期（AERP），AF诱导和电传导。房颤定义为不规则、快速心房搏动> 500 bpm，持续> 1000 ms。进行超声心动图、苏木精和伊红染色、Masson三色染色和天狼猩红染色，以评估心房结构的变化并检测纤维化。Western blotting和PCR检测TGF-β 1、I型胶原和III型胶原蛋白和mRNA表达的变化。结果LAD ≥ 40 mm的患者β 1ARAb水平高于LAD较小的患者（8.87 +/- 3.16 vs. 6.75 +/- 1.34 ng/mL，P = 0.005）。β 1ARAb水平与LAD和循环生物标志物水平呈正相关（均P < 0.05）。与对照组相比，免疫组家兔心率加快，AERP缩短（70.00 +/- 5.49 vs. 96.46 +/- 3.27 ms，P < 0.001），增加AF诱导（2）左前降支扩大，收缩功能障碍加重;（3）Masson三色染色显示左心房明显纤维化（15.17 +/- 3.46 vs. 4.92 +/-1.72%，P < 0.001）和天狼星红染色（16.76 +/-6.40vs.4.85 +/-0.40%，P < 0.001）;和（4）TGF-β 1、胶原I和胶原III的表达水平增加。结论β 1ARAbs参与了AF的发生发展，其可能机制与促进心房纤维化有关。
Objective Beta 1-adrenergic receptor autoantibodies (beta 1ARAbs) have been identified as a pathogenic factor in atrial fibrillation (AF), but the underlying pathogenetic mechanism is not well understood. We assessed the hypothesis that elevated beta 1ARAb levels increase AF susceptibility by promoting atrial fibrosis. Methods A total of 70 patients with paroxysmal AF were continuously recruited. The serum levels of beta 1ARAb and circulating fibrosis biomarkers were analyzed by ELISA. Linear regression was used to examine the correlations of beta 1ARAb levels with left atrial diameter (LAD) and circulating fibrosis biomarker levels. Furthermore, we established a rabbit beta 1ARAb overexpression model. We conducted electrophysiological studies and multielectrode array recordings to evaluate the atrial effective refractory period (AERP), AF inducibility and electrical conduction. AF was defined as irregular, rapid atrial beats > 500 bpm for > 1000 ms. Echocardiography, hematoxylin and eosin staining, Masson's trichrome staining, and picrosirius red staining were performed to evaluate changes in atrial structure and detect fibrosis. Western blotting and PCR were used to detect alterations in the protein and mRNA expression of TGF-beta 1, collagen I and collagen III. Results Patients with a LAD >= 40 mm had higher beta 1ARAb levels than patients with a smaller LAD (8.87 +/- 3.16 vs. 6.75 +/- 1.34 ng/mL, P = 0.005). beta 1ARAb levels were positively correlated with LAD and circulating biomarker levels (all P < 0.05). Compared with the control group, the rabbits in the immune group showed the following: (1) enhanced heart rate, shortened AERP (70.00 +/- 5.49 vs. 96.46 +/- 3.27 ms, P < 0.001), increased AF inducibility (55% vs. 0%, P < 0.001), decreased conduction velocity and increased conduction heterogeneity; (2) enlarged LAD and elevated systolic dysfunction; (3) significant fibrosis in the left atrium identified by Masson's trichrome staining (15.17 +/- 3.46 vs. 4.92 +/- 1.72%, P < 0.001) and picrosirius red staining (16.76 +/- 6.40 vs. 4.85 +/- 0.40%, P < 0.001); and (4) increased expression levels of TGF-beta 1, collagen I and collagen III. Conclusion Our clinical and experiential studies showed that beta 1ARAbs participate in the development of AF and that the potential mechanism is related to the promotion of atrial fibrosis.