The Role of Epicardial Adipose Tissue Inflammation in Post-Operative Atrial Fibrillation

心外膜脂肪组织炎症在术后房颤中的作用

• 批准号: MR/T008059/1
• 负责人: Vishal Vyas
• 金额: $ 23.4万
• 依托单位: Queen Mary University of London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FT008059%2F1
• 关键词: Role; Epicardial; Adipose; Tissue; Inflammation

Atrial fibrillation (AF) is the most common sustained heart rhythm disorder with significant associated morbidity including the risk of blood clots, stroke and heart failure alongside an increase in mortality. However, the precise causes of AF remain largely unknown. Recent studies suggest that generalised inflammation caused by circulating white blood cells may have a role in altering the properties of the heart to make it more susceptible to develop the abnormal electrical conduction of AF. Compelling data also shows that the layer of fat immediately surrounding the heart, known as epicardial adipose tissue (EAT), plays a key role in regulating the heart in health and disease. Putative roles of EAT in health include heat regulation, storage of energy and mechanical support to the heart. Given the proximity of EAT to the heart, it is also thought to be a critical link in mediating the effects of obesity on the heart. Hence, it has become a matter of intense medical interest to work out how and to what extent EAT can influence the heart tissue in disease states. EAT hosts a multitude of white blood cells which can produce inflammatory mediators that can easily pass into the heart. In turn, this can result in deleterious consequences such as inducing abnormal electrical impulses that may form the trigger for AF. Here, we propose to characterise the types of white blood cells and inflammatory mediators that play a role in the EAT-AF cascade in a cohort of patients undergoing open heart surgery. AF is the principal post-operative complication in patients undergoing heart surgery and carries specific additional short and long-term risks, including an elevated risk of stroke, death and increased length of hospitalisation with associated heightened health care costs. Hence, treatment strategies to reduce post-operative AF are of paramount importance.Our initial data indicates that a specific type of white blood cells (known as T cells) are elevated in patients who develop post-operative AF in addition to an elevation in markers characteristic of inflammation. In this project, we verify that the T cells identified in our initial analysis are responsible for the production of these elevated inflammatory markers. This will be performed in those patients who remain in normal heart rhythm post-operatively and those who develop AF (post-operative incidence of AF is in the order of 30-50%). Second, we will perform a detailed analysis of a host of inflammation markers to determine if they are increased in patients who develop new post-operative AF compared to patients who remain in normal heart rhythm post-operatively and those with longstanding AF. On identifying and verifying the specific immune parameters that are different we will aim to investigate their individual effect on the electrical properties of heart cells. Moreover, we will microscopically assess the heart tissue to look for abnormal immune cell infiltration into the heart itself. Finally, we will correlate these inflammatory and electrical alterations with detailed demographic and medical histories of patients. Ultimately, the project should form the basis of novel targets to reduce the incidence of post-operative AF.

心房颤动（AF）是最常见的持续性心律失常，具有显著的相关发病率，包括血栓、中风和心力衰竭的风险，以及死亡率的增加。然而，AF的确切原因在很大程度上仍然未知。最近的研究表明，由循环白色血细胞引起的全身炎症可能在改变心脏的特性方面发挥作用，使其更容易发展为AF的异常电传导。令人信服的数据还表明，心脏周围的脂肪层，称为心外膜脂肪组织（EAT），在健康和疾病中调节心脏方面起着关键作用。EAT在健康中的假定作用包括热量调节，能量储存和对心脏的机械支持。鉴于EAT与心脏的接近性，它也被认为是介导肥胖对心脏影响的关键环节。因此，研究EAT如何以及在多大程度上影响疾病状态下的心脏组织已经成为一个强烈的医学兴趣问题。EAT宿主大量的白色血细胞，这些细胞可以产生容易进入心脏的炎症介质。反过来，这可能会导致有害的后果，如诱导异常的电脉冲，可能形成触发AF。在这里，我们建议将类型的白色血细胞和炎症介质中发挥作用的EAT-AF级联在接受心脏直视手术的患者队列。AF是接受心脏手术的患者的主要术后并发症，并具有特定的额外短期和长期风险，包括卒中、死亡和住院时间延长的风险增加，以及相关的医疗保健费用增加。因此，减少术后AF的治疗策略是至关重要的。我们的初步数据表明，一种特定类型的白色血细胞（称为T细胞）在术后AF患者中升高，除了炎症标志物的升高。在这个项目中，我们验证了在我们的初步分析中鉴定的T细胞负责产生这些升高的炎症标志物。这将在术后保持正常心律的患者和发生AF的患者（术后AF发生率约为30-50%）中进行。其次，我们将对一系列炎症标志物进行详细分析，以确定与术后保持正常心律的患者和长期AF患者相比，术后新发AF患者的炎症标志物是否增加。在识别和验证不同的特定免疫参数时，我们将旨在研究其对心脏细胞电特性的个体影响。此外，我们将通过显微镜评估心脏组织，以寻找异常的免疫细胞浸润到心脏本身。最后，我们将把这些炎症和电变化与患者的详细人口统计学和病史联系起来。最终，该项目应形成新靶点的基础，以降低术后AF的发生率。

项目成果

Isolation of stromal vascular fraction cell suspensions from mouse and human adipose tissues for downstream applications.

• DOI: 10.1016/j.xpro.2021.100422
• 发表时间: 2021-06-18
• 期刊: STAR protocols
• 作者: Hearnden R;Sandhar B;Vyas V;Longhi MP
• 通讯作者: Longhi MP

Obesity and diabetes are major risk factors for epicardial adipose tissue inflammation.

• DOI: 10.1172/jci.insight.145495
• 发表时间: 2021-08-23
• 期刊: JCI insight
• 影响因子: 8
• 作者: Vyas V;Blythe H;Wood EG;Sandhar B;Sarker SJ;Balmforth D;Ambekar SG;Yap J;Edmondson SJ;Di Salvo C;Wong K;Roberts N;Uppal R;Adams B;Shipolini A;Oo AY;Lawrence D;Kolvekar S;Lall KS;Finlay MC;Longhi MP
• 通讯作者: Longhi MP

BS6 Deciphering the local immune lanscape in atrial fibrillation: the role of tissue-resident T cells

BS6 破译心房颤动中的局部免疫景观：组织驻留 T 细胞的作用

• DOI: 10.1136/heartjnl-2022-bcs.186
• 发表时间: 2022
• 作者: Vyas V

BS-400-05 EPICARDIAL ADIPOSE TISSUE-RESIDENT MEMORY T CELLS: A NOVEL INFLAMMATORY SIGNATURE IN ATRIAL FIBRILLATION

BS-400-05 心外膜脂肪组织驻留记忆 T 细胞：心房颤动中的一种新型炎症特征

• DOI: 10.1016/j.hrthm.2022.03.1204
• 发表时间: 2022
• 期刊: Heart Rhythm
• 影响因子: 5.5
• 作者: Vyas V