Interleukin-11 Is Elevated in Patients with Atrial Fibrillation, Correlates with Serum Fibrosis Markers, and Represents a Therapeutic Target for Atrial Fibrosis

被引:6
作者
Cong, Xinpeng [1 ]
Tian, Bei [1 ]
Zhu, Xi [1 ]
Zhang, Xiaogang [1 ]
Gu, Wei [1 ]
Zhao, Hanjun [1 ]
Hao, Shuwen [1 ]
Ning, Zhongping [1 ]
机构
[1] Shanghai Hlth Med Coll, Zhoupu Hosp, Dept Cardiol, Shanghai, Peoples R China
关键词
Atrial fibrillation; Atrial fibrosis; Interleukin-11; RECOMBINANT HUMAN INTERLEUKIN-11; EPIDEMIOLOGY; FIBROBLASTS; ACTIVATION; IL-11;
D O I
10.1159/000527740
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Introduction: Inflammatory cytokines are closely associated with developing cardiac fibrosis. This research aimed to explore the significant role of IL-11 in atrial fibrosis progression and potential therapeutic targets. Methods: 207 AF patients and 160 healthy subjects were included in the case-control study. Blood samples were analyzed for the level of IL-11 by enzyme-linked immunosorbent assay (ELISA). Angiotensin II (Ang II)-treated fibrosis mouse models were generated, and expression of IL-11 mRNA and protein was detected by RT-qPCR and Western blot. IL-11 antagonist was used to evaluating atrial fibrosis-related markers. Results: The persistent atrial fibrillation patients (n = 76) had significantly larger left atrial size, higher serum levels of hypertrophic protein BNP, proinflammatory cytokine high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6) compared to paroxysmal atrial fibrillation patients (n = 131), and healthy subjects (all p < 0.05). Pearson correlation analysis revealed significant positive correlation between serum IL-11 and cardiac fibrosis markers BNP (r = 0.394, p < 0.001), CTX-I (r = 0.418, p < 0.001), PICP (r = 0.306, p < 0.001), PIIINP (r = 0.335, p < 0.001), and TGF-beta 1 (r = 0.273, p < 0.001). In the fibrosis mouse model, Ang II infusion significantly upregulated IL-11 mRNA and protein expression in the left atrium of mice (p < 0.05), as well as staining intensity of Masson trichrome, the intensity of alpha-SMA, and it increased mRNA expression of collagen I and III in atrial tissue. IL-11 antagonist treatment significantly attenuated Masson trichrome, number of alpha-SMA-positive myofibroblasts in atrial tissue. Also, it significantly reduced the p-ERK1/2 in atrial tissue of mice infused with Ang II (p < 0.05). Conclusions: IL-11 is upregulated in the serum of AF patients, and IL-11 inhibitor significantly inhibited Ang II-induced atrial fibrosis, a key pathological feature of AF. Therefore, IL-11 could be a potential therapeutic target for AF.
引用
收藏
页码:575 / 586
页数:12
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