Correlation of plasma TSG-6 with cardiac function, myocardial fibrosis, and prognosis in dilated cardiomyopathy patients with heart failure.

Tumor necrosis factor α stimulated gene 6 (TSG-6) protein is an inflammation-inducing protein. In recent years, TSG-6 protein has been found to play an anti-inflammatory and anti-fibrosis role in a variety of disease models. The level of TSG-6 protein in circulating blood is considered to be a biological indicator for the evaluation of acute coronary syndrome, severe infection, and other diseases, and it is closely related to the prognosis. The clinical correlation between TSG-6 protein and dilated cardiomyopathy (DCM) patients with heart failure has not been reported. This study aims to investigate the changes of plasma TSG-6 protein levels in cardiomyopathy patients with heart failure and its correlation with cardiac function, myocardial fibrosis, and prognosis.Based on the prospective studies, a number of 90 DCM patients with heart failure were selected as a DCM heart failure group from Dec.1, 2019 to Sept.1, 2020. Thirty-nine healthy people were served as a control group. Plasma TSG-6, Collagen Ⅰ, Collagen III, and α-smooth muscle actin (α-SMA) were measured with ELISA test. Echocardiography was used to evaluate the structure and function of the heart. DCM patients with heart failure were followed up for 3 months. The patients were assigned into 2 groups according to whether they had major adverse cardiovascular events (MACE). The general clinical data, plasma TSG-6, Collagen Ⅰ, Collagen III, and α-SMA protein levels were compared between the control group and the DCM heart failure group. At the same time, the correlation between plasma TSG-6 protein level and cardiac function grade, myocardial fibrosis or prognosis of patients in the DCM heart failure group was analyzed.Compared with the control group, the heart rate, TSG-6, Collagen Ⅰ, Collage III, α-SMA, hemoglobin, atrial natriuretic peptide (NT-proBNP), hypersensitive C-reactive protein, aspartate aminotransferase, serum creatinine, lactate dehydrogenase, and left ventricular end diastolic diameter (LVEDD) increased significantly (all P<0.001). High-density lipoprotein, left ventricular short axis shortening rate (LVFS), and left ventricular ejection fraction (LVEF) decreased significantly in the DCM heart failure group (all P<0.001). Plasma levels of TSG-6 were positively correlated with NT-proBNP, Collagen Ⅰ, Collagen III, α-SMA, and LVEDD (all P<0.001), while they were negatively correlated with LVFS and LVEF (all P<0.001). With the increase of NYHA heart function classification, plasma levels of TSG-6, Collagen Ⅰ, Collagen III, and α-SMA increased significantly (all P<0.001). The increases in plasma levels of NT-proBNP and TSG-6 was associated with poor prognosis in DCM patients with heart failure (all P<0.05). The sensitivity and specificity of plasma NT-proBNP for evaluating the prognosis of DCM heart failure were 76.2% and 68.1%, respectively. The sensitivity and specificity of plasma TSG-6 for evaluating the prognosis of DCM heart failure were 95.2% and 66.7%, respectively. The sensitivity and specificity of plasma TSG-6 combined with NT-proBNP for prognostic evaluation of DCM heart failure were 85.7% and 81.2%, respectively. The specificity of plasma TSG-6 combined with NT-proBNP for the prognosis of heart failure was better than that of NT-proBNP or TSG-6 alone (P<0.001).The plasma levels TSG-6 in DCM patients with heart failure increase significantly, and the plasma levels TSG-6 could be used as a new predictor for cardiac function, myocardial fibrosis, and prognosis.目的: 肿瘤坏死因子α刺激基因-6(tumor necrosis factor α stimulated gene 6，TSG-6)蛋白是一种炎症诱导蛋白质。近年来发现TSG-6蛋白在多种疾病模型中发挥了抗炎、抗纤维化作用。在循环血液中TSG-6蛋白水平目前被认为可作为评估急性冠脉综合征、重症感染等疾病的生物学指标，并与预后密切相关。TSG-6蛋白与扩张型心肌病(以下简称扩心病)心力衰竭(以下简称心衰)临床相关性研究鲜见报道。本研究旨在探讨扩心病心衰患者血浆TSG-6蛋白水平变化及其与心功能、心肌纤维化及预后的相关性。方法: 采用前瞻性研究方法，连续选取2019年12月1日至2020年9月1于中南大学湘雅医院心内科住院的扩心病心衰患者90例作为扩心病心衰组，选择同期体检中心健康体检者39例作为对照组。采用ELISA法测定血浆TSG-6蛋白、Ⅰ型胶原蛋白(Collagen Ⅰ)、III型胶原蛋白(Collagen III)、α-平滑肌肌动蛋白(α-smooth muscle actin，α-SMA)的水平。采用超声心动图评估心脏的结构和功能。对扩心病心衰组患者随访3个月，根据是否发生主要不良心血管事件(major adverse cardiovascular events，MACE)，将患者分为发生MACE组及未发生MACE组。比较对照组与扩心病心衰组之间的一般临床资料，血浆TSG-6、Collagen Ⅰ、Collagen III、α-SMA蛋白水平差异，同时分析扩心病心衰组内血浆TSG-6蛋白水平与患者心功能分级、心肌纤维化及预后的相关性。结果: 与对照组相比，扩心病心衰组患者心率、TSG-6、Collagen Ⅰ、Collagen III、α-SMA、血红蛋白、心房脑钠肽前体(N-terminal pro-brain natriuretic peptide，NT-pro-BNP)、超敏C反应蛋白、谷草转氨酶、血清肌酐、乳酸脱氢酶和左心室舒张末期内径(left ventricular end diastolic diameter，LVEDD)显著升高(均P<0.001)，高密度脂蛋白、左心室短轴缩短率(left ventricular fractional shortening，LVFS)、左心室射血分数(left ventricular ejection fractions，LVEF)显著下降(均 P<0.001)。随着NYHA心功能分级的增加，血浆TSG-6、Collagen Ⅰ、Collagen III、α-SMA的水平显著升高(均P<0.001)。扩心病心衰患者血浆TSG-6水平与NT-proBNP、Collagen Ⅰ、Collagen III、α-SMA、LVEDD呈正相关(均P<0.001)，与LVFS和LVEF呈负相关(均P<0.001)。血浆NT pro-BNP和TSG-6水平升高均与心衰患者预后不佳相关(均 P<0.05)。血浆NT-proBNP水平对心衰预后评估的灵敏度为76.2%，特异度为68.1%；血浆TSG-6对心衰预后评估的灵敏度为95.2%，特异度为66.7%；血浆TSG-6联合NT-proBNP对心衰预后评估的灵敏度为85.7%，特异度为81.2%。血浆TSG-6联合NT-proBNP对心力衰竭预后的特异度优于单独应用NT-proBNP或TSG-6(均P<0.001)。结论: 扩心病心衰患者血浆TSG-6水平显著升高；血浆TSG-6水平可作为扩心病患者心功能分级严重程度、心肌纤维化以及预后新的预测因子。.