Oxidative damage to mitochondrial DNA in atrial muscle of patients with atrial fibrillation

Po Han Lin, Shih Huang Lee, Chia Ping Su, Yau Huei Wei

研究成果: 雜誌貢獻文章同行評審

114 引文 斯高帕斯(Scopus)

摘要

Atrial fibrillation (AF) is the most common cause of arrhythmia and is an aging-related disease encountered in clinical practice. The electrophysiological remolding with Ca2+ 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.

原文英語
頁(從 - 到)1310-1318
頁數9
期刊Free Radical Biology and Medicine
35
發行號10
DOIs
出版狀態已發佈 - 11月 15 2003
對外發佈

ASJC Scopus subject areas

  • 生物化學
  • 生理學(醫學)

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