Obesity and diabetes are major risk factors for epicardial adipose tissue inflammation.
Obesity and diabetes are major risk factors for epicardial adipose tissue inflammation.
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DOI：
10.1172/jci.insight.145495
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发表时间：
2021-08-23
期刊：
影响因子：
8
通讯作者：
Longhi MP
中科院分区：
文献类型：
--
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
心外膜脂肪组织（EAT）直接覆盖在心肌上，其形态和体积的变化与无数心血管和代谢疾病相关。然而，EAT的免疫结构和细胞特征仍然没有完全描述。我们的目的是确定EAT在人类中的免疫表型，并在瘦，肥胖和糖尿病患者中比较这些特征。我们招募了152名接受开胸冠状动脉旁路移植术（CABG）、瓣膜修复/置换术（VR）或CABG/VR联合手术的患者。收集患者的临床和生化数据以及EAT、皮下脂肪组织（SAT）和术前血液样本。通过流式细胞术评估免疫细胞谱，并通过免疫介质的基因表达研究进行补充。在EAT中跨代谢谱进行批量RNA-Seq，以评估在瘦、肥胖和糖尿病组中观察到的全转录组变化。流式细胞仪分析表明EAT高度富集于获得性免疫（T和B）细胞中。尽管超重/肥胖和糖尿病患者的EAT细胞特征与瘦对照患者相似，但EAT显示免疫介质（包括IL-1、IL-6、TNF-α和IFN-γ）的表达显著升高（P ≤ 0.01）。在SAT或血液中未观察到这些变化。无论是潜在的冠状动脉疾病还是高血压的存在都没有显著改变所观察到的免疫特征。批量RNA-Seq显示，与瘦对照相比，超重/肥胖患者的EAT中代谢和炎症途径发生了显著改变。适应性免疫细胞是人EAT和SAT中的主要免疫细胞成分。潜在的心脏代谢疾病的存在，特别是肥胖和糖尿病，而不是心脏病表型似乎改变了EAT的炎症特征。肥胖状态显著改变EAT代谢和炎症信号传导基因，强调肥胖对EAT转录组谱的影响。Barts Charity MGU 0413、Abbott、医学研究理事会MR/T008059/1和英国心脏基金会FS/13/49/30421和PG/16/79/32419。
Epicardial adipose tissue (EAT) directly overlies the myocardium, with changes in its morphology and volume associated with myriad cardiovascular and metabolic diseases. However, EAT’s immune structure and cellular characterization remain incompletely described. We aimed to define the immune phenotype of EAT in humans and compare such profiles across lean, obese, and diabetic patients. We recruited 152 patients undergoing open-chest coronary artery bypass grafting (CABG), valve repair/replacement (VR) surgery, or combined CABG/VR. Patients’ clinical and biochemical data and EAT, subcutaneous adipose tissue (SAT), and preoperative blood samples were collected. Immune cell profiling was evaluated by flow cytometry and complemented by gene expression studies of immune mediators. Bulk RNA-Seq was performed in EAT across metabolic profiles to assess whole-transcriptome changes observed in lean, obese, and diabetic groups. Flow cytometry analysis demonstrated EAT was highly enriched in adaptive immune (T and B) cells. Although overweight/obese and diabetic patients had similar EAT cellular profiles to lean control patients, the EAT exhibited significantly (P ≤ 0.01) raised expression of immune mediators, including IL-1, IL-6, TNF-α, and IFN-γ. These changes were not observed in SAT or blood. Neither underlying coronary artery disease nor the presence of hypertension significantly altered the immune profiles observed. Bulk RNA-Seq demonstrated significant alterations in metabolic and inflammatory pathways in the EAT of overweight/obese patients compared with lean controls. Adaptive immune cells are the predominant immune cell constituent in human EAT and SAT. The presence of underlying cardiometabolic conditions, specifically obesity and diabetes, rather than cardiac disease phenotype appears to alter the inflammatory profile of EAT. Obese states markedly alter EAT metabolic and inflammatory signaling genes, underlining the impact of obesity on the EAT transcriptome profile. Barts Charity MGU0413, Abbott, Medical Research Council MR/T008059/1, and British Heart Foundation FS/13/49/30421 and PG/16/79/32419.
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影响因子：
29
作者：
Li T;Zhang Z;Kolwicz SC Jr;Abell L;Roe ND;Kim M;Zhou B;Cao Y;Ritterhoff J;Gu H;Raftery D;Sun H;Tian R
通讯作者：
Tian R
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影响因子：
32.4
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O'Sullivan, David;van der Windt, Gerritje J. W.;Huang, Stanley Ching-Cheng;Curtis, Jonathan D.;Chang, Chih-Hao;Buck, Michael D.;Qiu, Jing;Smith, Amber M.;Lam, Wing Y.;DiPlato, Lisa M.;Hsu, Fong-Fu;Birnbaum, Morris J.;Pearce, Edward J.;Pearce, Erika L.
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Pearce, Erika L.
影响因子：
10.8
作者：
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通讯作者：
Harrison DG
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37.8
作者：
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影响因子：
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作者：
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