Epicardial Adipose Tissue-Derived IL-1β Triggers Postoperative Atrial Fibrillation.
Epicardial Adipose Tissue-Derived IL-1β Triggers Postoperative Atrial Fibrillation.
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DOI：
10.3389/fcell.2022.893729
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发表时间：
2022
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
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背景和目的：术后心房颤动(POAF)是指术后即刻新发的房颤，与不良心血管事件和永久性房颤的风险较高相关。导致POAF的机制尚不完全清楚，心外膜脂肪组织(EAT)炎症可能是一个强有力的触发因素。在这里，我们的目的是在一组冠心病患者中探索EAT分泌的白细胞介素1(IL)-1β、心房重构和房颤之间的联系。方法：收集40例接受心脏手术的冠心病患者的EAT和心房活检标本。对血清标本和EAT条件培养液进行IL-1β和IL-1ra的筛选。组织学评价心房纤维化程度。通过体外培养的人心房成纤维细胞暴露于IL-1、β和IL-18，探讨NLRP3炎性小体激活在促进纤维化中的潜在作用。结果：40%的患者出现POAF。有POAF和无POAF的患者在临床和超声心动图参数上是一致的，包括左房容量和EAT厚度。在组织学上，POAF与心房纤维化无关。两组患者血清IL-1、β和IL-1ra水平差异无统计学意义。POAF组EAT介导的IL-1β的分泌和表达明显高于非POAF组。体外实验表明，IL-1β和IL-18均能促进成纤维细胞的增殖和胶原合成。此外，受刺激的细胞通过产生IL-1β和转化生长因子-β来维持炎症和纤维化。结论：EAT在POAF的发生和心房纤维化重构中可能起到一定的作用。
Background and aims: Post-operative atrial fibrillation (POAF), defined as new-onset AF in the immediate period after surgery, is associated with poor adverse cardiovascular events and a higher risk of permanent AF. Mechanisms leading to POAF are not completely understood and epicardial adipose tissue (EAT) inflammation could be a potent trigger. Here, we aim at exploring the link between EAT-secreted interleukin (IL)-1β, atrial remodeling, and POAF in a population of coronary artery disease (CAD) patients. Methods: We collected EAT and atrial biopsies from 40 CAD patients undergoing cardiac surgery. Serum samples and EAT-conditioned media were screened for IL-1β and IL-1ra. Atrial fibrosis was evaluated at histology. The potential role of NLRP3 inflammasome activation in promoting fibrosis was explored in vitro by exposing human atrial fibroblasts to IL-1β and IL-18. Results: 40% of patients developed POAF. Patients with and without POAF were homogeneous for clinical and echocardiographic parameters, including left atrial volume and EAT thickness. POAF was not associated with atrial fibrosis at histology. No significant difference was observed in serum IL-1β and IL-1ra levels between POAF and no-POAF patients. EAT-mediated IL-1β secretion and expression were significantly higher in the POAF group compared to the no-POAF group. The in vitro study showed that both IL-1β and IL-18 increase fibroblasts’ proliferation and collagen production. Moreover, the stimulated cells perpetuated inflammation and fibrosis by producing IL-1β and transforming growth factor (TGF)-β. Conclusion: EAT could exert a relevant role both in POAF occurrence and in atrial fibrotic remodeling.