纤溶酶原激活物抑制物-1 在阵发性和持续性心房颤动中的作用。

The role of pro-fibrotic biomarkers in paroxysmal and persistent atrial fibrillation.

机构信息

Institute of Oncology Bucharest, Department of Carcinogenesis and Molecular Biology, 252 Fundeni, 022338 Bucharest, Romania.

Clinic Emergency Hospital Bucharest, Department of Cardiology, 8 Calea Floreasca, 014461 Bucharest, Romania.

出版信息

Cytokine. 2018 Mar;103:63-68. doi: 10.1016/j.cyto.2017.12.026. Epub 2018 Jan 8.

DOI:10.1016/j.cyto.2017.12.026

PMID:29324263

Abstract

PURPOSE

Signaling pathways involved in electrical, structural and contractile remodeling processes behind development and progression of atrial fibrillation (AF) have not been completely elucidated, but it seems to be related to complex interactions among neurohormonal and cellular mediators. We aimed to investigate interleukin-6 (IL-6), transforming growth factor-beta1 (TGF-β1), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), as biomarkers of atrial remodeling, in patients with paroxysmal and persistent AF, and their correlation with N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and left atrial (LA) diameter.

METHODS

Thirty-seven patients (22M/15F) with paroxysmal AF, 32 patients (22M/10F) with persistent AF and 30 healthy control subjects (18M/12F) were enrolled in the study. Serum levels of biomarkers were measured by ELISA. Cardiac function was assessed echocardiographically.

RESULTS

IL-6 levels and MMP-9/TIMP-1 ratio were significantly higher in AF patients than in non-AF controls (P < .001), and in persistent than in paroxysmal AF (P < .001), in line with NT-proBNP and LA diameter. In contrast, TGF-β1levels declined with increasing AF duration (from 51.2 pg/mL, IQR: 38.9-87.9 pg/mL in paroxysmal to 23.9 pg/mL, IQR: 16.9-43.6 pg/mL in persistent AF). TGF-β1 was negatively correlated with NT-proBNP (r = -0.53, P = .001 in paroxysmal AF and r = -0.71, P < .001 in persistent AF) and LA diameter (r = -0.44, P = .006 in paroxysmal AF and r = -0.51, P = .003 in persistent AF).

CONCLUSIONS

Our results demonstrate that AF development and progression (from paroxysmal to persistent) is associated with a gradual increase in serum levels of NT-proBNP, IL-6 and MMP-9/TIMP-1 ratio. Moreover, this study suggests that the relationship between TGF-β1, NT-proBNP and LA diameter allows for the progression of atrial remodeling during AF, despite compensatory changes in the TGF-β1 signaling pathway.

摘要

目的

尽管转化生长因子-β1（TGF-β1）信号通路发生代偿性变化，但与神经激素和细胞介质之间复杂相互作用有关的离子通道、结构和收缩重构过程背后的心房颤动（AF）发生和发展的信号通路尚未完全阐明。我们旨在研究白细胞介素-6（IL-6）、转化生长因子-β1（TGF-β1）、基质金属蛋白酶-9（MMP-9）、金属蛋白酶组织抑制剂-1（TIMP-1）作为阵发性和持续性 AF 患者心房重构的生物标志物，及其与氨基末端脑钠肽前体（NT-proBNP）和左心房（LA）直径的相关性。

方法

研究纳入 37 例阵发性 AF 患者（22 例男性/15 例女性）、32 例持续性 AF 患者（22 例男性/10 例女性）和 30 例健康对照者（18 例男性/12 例女性）。通过 ELISA 测定生物标志物血清水平。超声心动图评估心功能。

结果

与非 AF 对照组相比，AF 患者的 IL-6 水平和 MMP-9/TIMP-1 比值显著升高（均 P<0.001），且持续性 AF 患者高于阵发性 AF 患者（均 P<0.001），与 NT-proBNP 和 LA 直径一致。相比之下，TGF-β1 水平随着 AF 持续时间的增加而降低（从阵发性 AF 的 51.2pg/ml（IQR：38.9-87.9pg/ml）到持续性 AF 的 23.9pg/ml（IQR：16.9-43.6pg/ml））。TGF-β1 与 NT-proBNP 呈负相关（阵发性 AF 中 r=-0.53，P=0.001；持续性 AF 中 r=-0.71，P<0.001）和 LA 直径（阵发性 AF 中 r=-0.44，P=0.006；持续性 AF 中 r=-0.51，P=0.003）。

结论

我们的研究结果表明，AF 的发生和发展（从阵发性到持续性）与血清 NT-proBNP、IL-6 和 MMP-9/TIMP-1 比值逐渐升高有关。此外，本研究提示 TGF-β1、NT-proBNP 和 LA 直径之间的关系可以在 AF 期间促进心房重构的进展，尽管 TGF-β1 信号通路发生代偿性变化。