8-hydroxy-2--deoxyguanosine and Atrial-Fibrillation

Previous studies revealed a relationship between 8-hydroxy-2'-deoxyguanosine (8-OHdG) and the occurrence/recurrence of atrial fibrillation (AF). This 2-part study aimed to validate whether DNA damage related to 8-OHdG is associated with left atrial (LA) fibrosis in AF patients quantified by voltage mapping (Part I), and to identify the underlying genetic components regulating the 8-OHdG level (Part II).Methods and Results: Plasma 8-OHdG determination, DNA extraction, and genotyping were conducted before catheter ablation. LA voltage mapping was performed under sinus rhythm. According to the percentage of low voltage area (LVA), patients were categorized as stage I (<5%), stage II (5-10%), stage III (10-20%), and stage IV (>20%). Part I included 209 AF patients. The 8-OHdG level showed an upward trend together with advanced LVA stage (stage I 8.1 [6.1, 10.5] ng/mL, stage II 8.5 [5.7, 14.1] ng/mL, stage III 14.3 [12.1, 16.5] ng/mL, stage IV 13.9 [10.5, 16.0] ng/mL, P<0.000). Part II included 175 of the 209 patients from Part I. Gene-set analysis based on genome-wide association study summary data identified that the gene set named 'DNA methylation on cytosine' was the only genetic component significantly associated with 8-OHdG concentration.. Higher 8-OHdG levels may predict more advanced LVA of the LA in AF patients. DNA methylation is the putative genetic component underlying oxidative DNA damage in AF patients.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Atrial Fibrillation; Biomarkers; Catheter Ablation; DNA Methylation; Fibrosis; Genome-Wide Association Study; Heart Atria; Humans; Recurrence; Treatment Outcome

Recent research findings have revealed a key role of oxidative DNA damage in the pathogenesis of atrial fibrillation (AF). Therefore, the circulating oxidative DNA damage marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) may represent a biomarker for staging AF and identifying patients at risk for AF recurrence and postoperative atrial fibrillation (POAF) after treatment.. The purpose of this study was to investigate whether serum levels of 8-OHdG correlate with the stage of AF, recurrence after AF treatment, and onset of POAF after cardiac surgery.. In this prospective observational study, 8-OHdG levels were detected by enzyme-linked immunosorbent assay in human serum samples. Blood samples were collected from control patients without AF history; patients with paroxysmal AF and persistent AF undergoing electrical cardioversion or pulmonary vein isolation (PVI); and patients with sinus rhythm (SR) undergoing cardiac surgery. AF recurrence was determined during 12-month follow-up. Univariate and multivariate analyses were used to identify changes in 8-OHdG levels between the groups.. Compared to the control group, 8-OHdG levels in the patient groups gradually and significantly increased during arrhythmia progression. 8-OHdG levels in AF patients showing AF recurrence after PVI treatment were significantly increased compared to patients without AF recurrence. Moreover, in SR patients undergoing cardiac surgery, 8-OHdG levels were significantly elevated in those showing POAF compared to patients without POAF.. 8-OHdG level may represent a potential diagnostic biomarker for AF staging as well as for predicting AF recurrence and POAF after treatment.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Atrial Fibrillation; Biomarkers; Cardiac Surgical Procedures; Electric Countershock; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prognosis; Prospective Studies; Treatment Outcome

Oxidative stress is considered to contribute to the pathological consequences of atrial fibrillation (AF). We examined the level of oxidative stress in AF patients and changes in its level following sinus rhythm restoration.. Oxidative stress level was evaluated by urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, and urinary biopyrrin, an oxidative metabolite of bilirubin. In Study 1, we compared 8-OHdG/creatinine levels between patients with permanent AF (AF-group, n=40) and sinus rhythm (SR-group, n=133). In Study 2, we examined the changes in 8-OHdG and biopyrrin levels in 36 patients with persistent AF following sinus rhythm restoration by electrical or pharmacological cardioversion (n=15) and radiofrequency catheter ablation (n=21).. In Study 1, 8-OHdG/creatinine levels were significantly higher in AF-group than in SR-group (19.1 ± 8.6 vs. 12.3 ± 5.5 ng/mg, p<0.001). Multivariate analysis showed that the presence of AF was an independent factor that significantly correlated with 8-OHdG/creatinine level after adjustment for other covariates to oxidative stress (β=0.36, p<0.001). Sinus rhythm was maintained at the chronic phase in patients of all Study 2 (7.2 ± 5.8 months after cardioversion or catheter ablation). 8-OHdG/creatinine and biopyrrin/creatinine levels at the chronic phase were significantly lower than those before cardioversion or catheter ablation (8.7 ± 3.2 vs. 21.7 ± 15.1 ng/mg, p<0.0001 and 1.7 ± 1.1 vs. 3.0 ± 1.9 mU/mg, p<0.0001).. Oxidative stress level is significantly increased in AF patients, but can be improved by restoration of sinus rhythm. The results suggest that the pathogenic process of AF is promoted by AF itself through the production of oxidative stress.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Aged, 80 and over; Atrial Fibrillation; Bilirubin; Biomarkers; Deoxyguanosine; Female; Follow-Up Studies; Heart Rate; Humans; Male; Middle Aged; Oxidative Stress; Treatment Outcome

Topics: 8-Hydroxy-2'-Deoxyguanosine; Atrial Fibrillation; Bilirubin; Deoxyguanosine; Female; Heart Rate; Humans; Male; Oxidative Stress

Atrial fibrillation (AF) is the most common cause of arrhythmia and is an aging-related disease encountered in clinical practice. The electrophysiological remolding with Ca(2+) overloading and cellular structure changes were found in cardiomyocytes of AF patients. In previous studies, increased oxidative stress and oxidative damage was found in cardiomyocytes during the ischemia/reperfusion injury. Besides, mitochondrial DNA (mtDNA) deletion and mtDNA proliferation occur frequently in affected tissues of patients with certain degenerative diseases and during aging of the human. However, it remains unclear whether high oxidative stress and alteration of mtDNA play a role in the pathophysiology of AF. In this study, we first screened for large-scale deletions of mtDNA in the atrial muscle of AF patients by long-range polymerase chain reaction (PCR). The results showed that large-scale deletions between nucleotide positions 7900 and 16500 of mtDNA occurred at a high frequency. Among them, the 4977 bp deletion was the most frequent and abundant one, and the mean proportion of mtDNA with the 4977 bp deletion in the atrial muscle of the patients with AF was 3.75-fold higher than that of the patients without AF (p <.005). Furthermore, quantitative PCR was performed to evaluate lesions in mtDNA caused by oxidative damage. We found that the degree of mtDNA damage in the patients with AF was greater than that of the patients without AF (3.29 vs.1.60 per 10 kb, p <.0005). The 8-OHdG, which is one of the most common products of oxidative damage to DNA, was also found at a higher frequency in mtDNA of patients with AF as compared with those without AF. In addition, the mtDNA content was found to increase significantly in the patients with AF (p =.0051). The level of mtDNA lesion and the mtDNA content was positively correlated (r = 0.44). These results suggest that oxidative injury and deletion of mtDNA in cardiac muscle are increased in the patients with AF, which may contribute to the impairment of bioenergetic function of mitochondria and induction of the oxidative vicious cycle involved in the pathogenesis of atrial myopathy in AF.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Atrial Fibrillation; Deoxyguanosine; DNA Damage; DNA, Mitochondrial; Heart Atria; Humans; Mitochondria, Heart; Muscle Fibers, Skeletal; Oxidation-Reduction; Oxidative Stress; Polymerase Chain Reaction; Sequence Deletion