Abstract:
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 (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. RESULTS: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. CONCLUSIONS:U-8-OHdG is a potentially clinically useful biomarker for evaluating inflammatory activity and monitoring the effectiveness of corticosteroid therapy in SAR patients.
journal_name
Int J Cardioljournal_title
International journal of cardiologyauthors
Kobayashi S,Myoren T,Oda S,Inari M,Ishiguchi H,Murakami W,Fukuda M,Tanaka T,Okuda S,Nao T,Doi M,Yamada J,Okamura T,Hoshii Y,Suga K,Matsuzaki M,Yano Mdoi
10.1016/j.ijcard.2015.04.144subject
Has Abstractpub_date
2015-01-01 00:00:00pages
319-28eissn
0167-5273issn
1874-1754pii
S0167-5273(15)00867-0journal_volume
190pub_type
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