Blood-based 8-hydroxy-2′-deoxyguanosine level: A potential diagnostic biomarker for atrial fibrillation

Li, Jin; Zhang, Deli; Ramos, Kennedy Silva; Baks, Luciënne; Wiersma, Marit; Lanters, Eva A.H.; Bogers, Ad J.J.C.; Groot, Natasja M.S. de; Brundel, Bianca J. J. M.

doi:10.1016/j.hrthm.2020.09.017

Cited by 24 publications

(19 citation statements)

References 33 publications

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“…Thus, SOD and GSH‐Px can reflect the body's ability to resist oxidative damage. Moreover, 8‐OHdG, a product of free radical‐induced oxidative damage, has been widely used as a marker for DNA damage and cardiovascular diseases 67,68 . Our results show that the levels of MDA and 8‐OHdG in hypertension patients increased, whereas SOD and GSH‐Px markedly decreased, indicating that oxidative stress occurred during the pathogenesis of hypertension in studied pedigrees.…”

Section: Discussionmentioning

confidence: 60%

Molecular characterization of two Chinese pedigrees with maternally inherited hypertension

Ding

Guo

et al. 2021

The Journal of Gene Medicine

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Background Mutations in mitochondrial tRNA (mt‐tRNA) genes are associated with hypertension, although their pathogenic mechanisms remain poorly understood. Methods In the present study, two Han Chinese families with maternally transmitted hypertension were interviewed. The mtDNA mutations of matrilineal relatives were screened by polymerase chain reaction‐Sanger sequencing. Mitochondrial ATP, membrane potential and reactive oxygen species (ROS) were also analyzed in polymononuclear leukocytes carrying these mt‐tRNA mutations. Additionally, the levels of oxidative stress‐related biomarkers [malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH‐Px) and 8‐hydroxy‐2‐deoxyguanosine (8‐OHdG)] were analyzed. Results Nine of 13 adult matrilineal relatives of these pedigrees exhibited a wide range of severity of hypertension. The age at onset of hypertension was 30–62 years (average 46 years). Mutational screening of mitochondrial genomes revealed tRNAArg T10410C and T10454C mutations. Indeed, the m.T10454C and m.T10410C mutations occurred at conserved bases of TΨC‐loop and acceptor arm of tRNAArg (positions 55 and 6), which are critical for tRNAArg post‐transcriptional modification. Thus, the defects in tRNA modification may cause failure in tRNA metabolism, impairing mitochondrial translation. Biochemical analysis revealed that m.T10454C or m.T10410C mutation significantly reduced mitochondrial ATP and membrane potential and also increased ROS production in mutant cell lines (all p < 0.05). In addition, the levels of MDA and 8‐OHdG in hypertensive patients markedly increased, whereas those of SOD and GSH‐Px decreased (all p < 0.05). Conclusions These findings demonstrate that m.T10410C and m.T10454C mutations affect the structure and function of tRNAArg and consequently alter mitochondrial function and lead to oxidative stress, which are involved in the pathogenesis of maternally inherited hypertension.

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Section: Discussionmentioning

confidence: 60%

Molecular characterization of two Chinese pedigrees with maternally inherited hypertension

Ding

Guo

et al. 2021

The Journal of Gene Medicine

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“…Additionally, some of them, such as 8-OHdG, do not show specificity for HD. Its level is also significantly increased in the course of other diseases, including cardiovascular pathology [154,155]. This is a common problem when determining potential biomarkers closely related to a specific disease entity, which complicates the interpretation of results and affects their credibility.…”

Section: Discussionmentioning

confidence: 99%

What, When and How to Measure—Peripheral Biomarkers in Therapy of Huntington’s Disease

Przybył

Woźna-Wysocka

Kozłowska

et al. 2021

IJMS

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Among the main challenges in further advancing therapeutic strategies for Huntington’s disease (HD) is the development of biomarkers which must be applied to assess the efficiency of the treatment. HD is a dreadful neurodegenerative disorder which has its source of pathogenesis in the central nervous system (CNS) but is reflected by symptoms in the periphery. Visible symptoms include motor deficits and slight changes in peripheral tissues, which can be used as hallmarks for prognosis of the course of HD, e.g., the onset of the disease symptoms. Knowing how the pathology develops in the context of whole organisms is crucial for the development of therapy which would be the most beneficial for patients, as well as for proposing appropriate biomarkers to monitor disease progression and/or efficiency of treatment. We focus here on molecular peripheral biomarkers which could be used as a measurable outcome of potential therapy. We present and discuss a list of wet biomarkers which have been proposed in recent years to measure pre- and postsymptomatic HD. Interestingly, investigation of peripheral biomarkers in HD can unravel new aspects of the disease pathogenesis. This especially refers to inflammatory proteins or specific immune cells which attract scientific attention in neurodegenerative disorders.

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“…In AF patients, an increase in oxidative DNA damage markers (i.e., 8-oxoG and 53BP1) [26] and differentially expressed proteins, closely related to oxidative stress-related signaling pathways [116], have been observed. Moreover, serum levels of 8-hydroxy-2 -deoxyguanosine (8-OHdG), a vital oxidative DNA damage by-product formed by exonucleases during DNA repair processes, positively correlate with AF progression, onset of postoperative AF (poAF), and recurrence after AF treatment [118], substantiating a role for oxidative stress-induced DNA damage in AF development. In the next part of this review, two major underlying biochemical events associated with oxidative DNA damage and repair in AF and a summary of novel therapeutic treatment implications for AF will be discussed.…”

Section: Oxidative Dna Damage and Repair In Afmentioning

confidence: 99%

Role of Oxidative DNA Damage and Repair in Atrial Fibrillation and Ischemic Heart Disease

Wang

Carmone

et al. 2021

IJMS

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Atrial fibrillation (AF) and ischemic heart disease (IHD) represent the two most common clinical cardiac diseases, characterized by angina, arrhythmia, myocardial damage, and cardiac dysfunction, significantly contributing to cardiovascular morbidity and mortality and posing a heavy socio-economic burden on society worldwide. Current treatments of these two diseases are mainly symptomatic and lack efficacy. There is thus an urgent need to develop novel therapies based on the underlying pathophysiological mechanisms. Emerging evidence indicates that oxidative DNA damage might be a major underlying mechanism that promotes a variety of cardiac diseases, including AF and IHD. Antioxidants, nicotinamide adenine dinucleotide (NAD+) boosters, and enzymes involved in oxidative DNA repair processes have been shown to attenuate oxidative damage to DNA, making them potential therapeutic targets for AF and IHD. In this review, we first summarize the main molecular mechanisms responsible for oxidative DNA damage and repair both in nuclei and mitochondria, then describe the effects of oxidative DNA damage on the development of AF and IHD, and finally discuss potential targets for oxidative DNA repair-based therapeutic approaches for these two cardiac diseases.

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Blood-based 8-hydroxy-2′-deoxyguanosine level: A potential diagnostic biomarker for atrial fibrillation

Cited by 24 publications

References 33 publications

Molecular characterization of two Chinese pedigrees with maternally inherited hypertension

Molecular characterization of two Chinese pedigrees with maternally inherited hypertension

What, When and How to Measure—Peripheral Biomarkers in Therapy of Huntington’s Disease

Role of Oxidative DNA Damage and Repair in Atrial Fibrillation and Ischemic Heart Disease

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