Urinary 8-hydroxy-2′-deoxyguanosine as a novel biomarker of inflammatory activity in patients with cardiac sarcoidosis
Urinary 8-hydroxy-2′-deoxyguanosine as a novel biomarker of inflammatory activity in patients with cardiac sarcoidosis
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DOI：
10.1016/j.ijcard.2015.04.144
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发表时间：
2015-07-01
影响因子：
3.5
通讯作者：
Yano, Masafumi
中科院分区：
文献类型：
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作者：
Kobayashi, Shigeki;Myoren, Takeki;Yano, Masafumi
背景：炎症和氧化应激在心脏结节病（SAR）的发病机制中起着至关重要的作用。我们研究了尿（U）8-羟基-2 '-脱氧鸟苷（8-OHdG）-一种氧化性DNA损伤标记物-是否与SAR炎症活动有关。在31名SAR患者中测量U-8-OHdG水平，根据F-18-氟脱氧葡萄糖正电子发射断层扫描-计算机断层扫描将其分为活动性（n=17）或非活动性（n=14（F-18-FDG-PET/CT），28名扩张型心肌病（DCM）患者和30名对照。在活动性SAR患者中，在皮质类固醇治疗后6个月重新检查U-8-OHdG水平并与F-18-FDG-PET/CT结果进行比较，以评估治疗反应。SAR患者左心室（LV）尸检样本的免疫组织化学检查显示，在PET/CT上显示F-18-FDG蓄积的LV切片心肌细胞核中8-OHdG染色阳性，活动性SAR患者冠状窦8-OHdG水平明显高于主动脉根部。SAR患者的U-8-OHdG水平高于对照组，活动性SAR患者的U-8-OHdG水平显著高于非活动性SAR和DCM患者。在受试者工作特征曲线分析中，U-8-OHdG是活性SAR的强有力预测因子（AUC，0.98; 95%CI，0.94-1.02;最佳临界值，13.1 ng/mg肌酐），灵敏度为88.2%，特异性为92.9%。U-8-OHdG水平显着下降，在6个月后皮质类固醇治疗开始，在局部心脏摄取F-18-FDG.Conclusions的减少成比例：U-8-OHdG是一个潜在的临床有用的生物标志物，用于评估炎症活动和监测皮质类固醇治疗SAR患者的有效性。(C)2015爱思唯尔爱尔兰有限公司版权所有。
Background: Inflammation and oxidative stress play a crucial role in the pathogenesis of cardiac sarcoidosis (SAR). We investigated whether urinary (U) 8-hydroxy-2'-deoxyguanosine (8-OHdG)-an oxidative DNA damage marker-was related to SAR inflammatory activity.Methods: U-8-OHdG levels were measured in 31 SAR patients, classified as active (n=17) or non-active (n=14) based on F-18-fluorodeoxyglucose positron emission tomography-computed tomography (F-18-FDG-PET/CT), 28 dilated cardiomyopathy (DCM) patients, and 30 controls. In active SAR patients, U-8-OHdG levels were reexamined and compared with F-18-FDG-PET/CT results at 6 months after corticosteroid treatment to assess therapeutic response.Results: Immunohistochemical examination of left ventricle (LV) autopsy samples from SAR patients revealed positive 8-OHdG staining in cardiomyocyte nuclei from LV sections showing F-18-FDG accumulation on PET/CT, while serum 8-OHdG levels were significantly higher in the coronary sinus than in the aortic root only in active SAR patients. U-8-OHdG levels in SAR patients were higher than those in controls, and significantly higher in active SAR patients than in non-active SAR and DCM patients. U-8-OHdG was a powerful predictor of active SAR in receiver operating characteristic curve analysis (AUC, 0.98; 95% CI, 0.94-1.02; optimal cutoff value, 13.1 ng/mg creatinine), with a sensitivity of 88.2% and a specificity of 92.9%. U-8-OHdG levels in responders significantly decreased at 6 months after corticosteroid treatment initiation, in proportion with the decrease in the focal cardiac uptake of F-18-FDG.Conclusions: U-8-OHdG is a potentially clinically useful biomarker for evaluating inflammatory activity and monitoring the effectiveness of corticosteroid therapy in SAR patients. (C) 2015 Elsevier Ireland Ltd. All rights reserved.