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冠心病患者心外膜脂肪组织脂肪细胞肥大与低度炎症和细胞外基质重塑生物标志物的关联

Association of Epicardial Adipose Tissue Adipocytes Hypertrophy with Biomarkers of Low-Grade Inflammation and Extracellular Matrix Remodeling in Patients with Coronary Artery Disease.

作者信息

Kologrivova Irina V, Naryzhnaya Natalia V, Koshelskaya Olga A, Suslova Tatiana E, Kravchenko Elena S, Kharitonova Olga A, Evtushenko Vladimir V, Boshchenko Alla A

机构信息

Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 111A Kievskaya, 634012 Tomsk, Russia.

出版信息

Biomedicines. 2023 Jan 17;11(2):241. doi: 10.3390/biomedicines11020241.

Abstract

The aim of the study was to compare the morphological features of epicardial adipose tissue (EAT) adipocyte with the circulating inflammatory biomarkers and parameters of extracellular matrix remodeling in patients with coronary artery disease (CAD). We recruited 42 patients with CAD (m/f 28/14) who were scheduled for coronary artery bypass graft surgery (CABG). EAT adipocytes were obtained by the enzymatic method from intraoperative adipose tissue samples. Concentrations of secreted and lipoprotein-associated phospholipase A2 (sPLA2 and LpPLA2), TNF-α, IL-1β, IL-6, IL-10, high-sensitive C-reactive protein (hsCRP), metalloproteinase-9 (MMP-9), MMP-2, C-terminal cross-linking telopeptide of type I collagen (CTX-I), and tissue inhibitor of metalloproteinase 1 (TIMP-1) were measured in blood serum. Patients were divided into two groups: group 1-with mean EAT adipocytes' size ≤ 87.32 μm; group 2-with mean EAT adipocytes' size > 87.32 μm. Patients of group 2 had higher concentrations of triglycerides, hsCRP, TNF-α, and sPLA2 and a lower concentration of CTX-I. A multiple logistic regression model was created (R = 0.43, = 0.0013). Concentrations of TNF-α, sPLA2 and CTX-I appeared to be independent determinants of the EAT adipocyte hypertrophy. ROC analysis revealed the 78% accuracy, 71% sensitivity, and 85% specificity of the model, AUC = 0.82. According to our results, chronic low-grade inflammation and extracellular matrix remodeling are closely associated with the development of hypertrophy of EAT adipocytes, with serum concentrations of TNF-α, sPLA2 and CTX-I being the key predictors, describing the variability of epicardial adipocytes' size.

摘要

本研究旨在比较冠心病(CAD)患者的心外膜脂肪组织(EAT)脂肪细胞的形态学特征与循环炎症生物标志物及细胞外基质重塑参数。我们招募了42例计划进行冠状动脉旁路移植术(CABG)的CAD患者(男/女为28/14)。通过酶法从术中获取的脂肪组织样本中获得EAT脂肪细胞。检测血清中分泌型和脂蛋白相关磷脂酶A2(sPLA2和LpPLA2)、TNF-α、IL-1β、IL-6、IL-10、高敏C反应蛋白(hsCRP)、金属蛋白酶-9(MMP-9)、MMP-2、I型胶原C末端交联端肽(CTX-I)和金属蛋白酶组织抑制剂1(TIMP-1)的浓度。患者分为两组:第1组——EAT脂肪细胞平均大小≤87.32μm;第2组——EAT脂肪细胞平均大小>87.32μm。第2组患者的甘油三酯、hsCRP、TNF-α和sPLA2浓度较高,而CTX-I浓度较低。建立了多元逻辑回归模型(R = 0.43,P = 0.0013)。TNF-α、sPLA2和CTX-I的浓度似乎是EAT脂肪细胞肥大的独立决定因素。ROC分析显示该模型的准确率为78%,灵敏度为71%,特异性为85%,曲线下面积(AUC)= 0.82。根据我们的研究结果,慢性低度炎症和细胞外基质重塑与EAT脂肪细胞肥大的发生密切相关,血清中TNF-α、sPLA2和CTX-I的浓度是描述心外膜脂肪细胞大小变异性的关键预测指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9609/9953115/3bc443436f5f/biomedicines-11-00241-g001.jpg

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