Kobayashi Shigeki, Myoren Takeki, Oda Seiko, Inari Makana, Ishiguchi Hironori, Murakami Wakako, Fukuda Masakazu, Tanaka Takeo, Okuda Shinichi, Nao Tomoko, Doi Masahiro, Yamada Jutaro, Okamura Takayuki, Hoshii Yoshinobu, Suga Kazuyoshi, Matsuzaki Masunori, Yano Masafumi
Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan.
Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan.
Int J Cardiol. 2015;190:319-28. doi: 10.1016/j.ijcard.2015.04.144. Epub 2015 Apr 17.
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.
U-8-OHdG levels were measured in 31 SAR patients, classified as active (n=17) or non-active (n=14) based on (18)F-fluorodeoxyglucose positron emission tomography-computed tomography ((18)F-FDG-PET/CT), 28 dilated cardiomyopathy (DCM) patients, and 30 controls. In active SAR patients, U-8-OHdG levels were reexamined and compared with (18)F-FDG-PET/CT results at 6 months after corticosteroid treatment to assess therapeutic response.
Immunohistochemical examination of left ventricle (LV) autopsy samples from SAR patients revealed positive 8-OHdG staining in cardiomyocyte nuclei from LV sections showing (18)F-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 (18)F-FDG.
U-8-OHdG is a potentially clinically useful biomarker for evaluating inflammatory activity and monitoring the effectiveness of corticosteroid therapy in SAR patients.
炎症和氧化应激在心脏结节病（SAR）的发病机制中起关键作用。我们研究了尿（U）8-羟基-2'-脱氧鸟苷（8-OHdG）——一种氧化性DNA损伤标志物——是否与SAR炎症活动相关。
测量了31例SAR患者、28例扩张型心肌病（DCM）患者和30例对照者的U-8-OHdG水平。根据（18）F-氟脱氧葡萄糖正电子发射断层扫描-计算机断层扫描（（18）F-FDG-PET/CT）将31例SAR患者分为活动期（n = 17）或非活动期（n = 14）。在活动期SAR患者中，在开始皮质类固醇治疗6个月后重新检测U-8-OHdG水平，并与（18）F-FDG-PET/CT结果进行比较，以评估治疗反应。
对SAR患者左心室（LV）尸检样本的免疫组织化学检查显示，PET/CT上显示（18）F-FDG摄取的LV切片心肌细胞核中8-OHdG染色呈阳性，而仅在活动期SAR患者中，冠状窦中的血清8-OHdG水平显著高于主动脉根部。SAR患者的U-8-OHdG水平高于对照组，活动期SAR患者显著高于非活动期SAR患者和DCM患者。在受试者工作特征曲线分析中，U-8-OHdG是活动期SAR的有力预测指标（AUC，0.98；95%CI，0.94 - 1.02；最佳截断值，13.1 ng/mg肌酐），敏感性为88.2%，特异性为92.9%。开始皮质类固醇治疗6个月后，反应者的U-8-OHdG水平显著下降，与（18）F-FDG的局部心脏摄取减少成比例。
U-8-OHdG是一种潜在的临床有用生物标志物，可用于评估SAR患者的炎症活动并监测皮质类固醇治疗的有效性。
