ArticleCirculation research2010
DNA damage links mitochondrial dysfunction to atherosclerosis and the metabolic syndrome.
Article in Circulation research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT03655704 (Apabetalone for Pulmonary Arterial Hypertension), which is not on this map. Cited by 107 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Apabetalone for Pulmonary Arterial Hypertension: a Pilot Study
Who cites it
107 citing papers in PubMed, 3 syntheses or guidelines pooled it, 238 citations in OpenAlex.
- Association of m.5178C>A variant with serum lipid levels: a systematic review and meta-analysis.Bioscience reports · 2021Pooled it
- 8-hydroxy-2'-deoxyguanosine and cardiovascular disease: a systematic review.Current atherosclerosis reports · 2014Pooled it
- Pooled it
- Multiomics Insights Linking Personal Care Products Exposure to Serum Lipid Profiles in Older Adults: The China BAPE Study.Environmental health perspectives · 2026Article
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- Integrative transcriptomic and machine learning approach reveals key DDR genes and predictors of ami risk in the Bangladeshi population.Scientific reports · 2026Article
- Targeting PANoptosis in atherosclerosis: bridging cell death mechanisms and therapy.Apoptosis : an international journal on programmed cell death · 2026Review
- Self-DNA by Activating the CGAS-STING1 Pathway Contributes to the Pathogenesis of Atherosclerosis.Current atherosclerosis reports · 2025Review
- Pathophysiological Mechanisms of Diabetes-Induced Macrovascular and Microvascular Complications: The Role of Oxidative Stress.Medical sciences (Basel, Switzerland) · 2025Review
- Nutritional status and metabolic alterations in patients with ataxia-telangiectasia.Orphanet journal of rare diseases · 2025Article
- Causes and consequences of DNA double-stranded breaks in cardiovascular disease.Molecular and cellular biochemistry · 2025Review
- The mitochondrial dysfunction, alongside the modifiable burden of traditional risk factors, drives the development of early-onset coronary artery disease.Frontiers in cardiovascular medicine · 2025Article
- Loss of DNA Polymerase β Delays Atherosclerosis inInternational journal of molecular sciences · 2024Article
- Mitochondrial Reactive Oxygen Species Dysregulation in Heart Failure with Preserved Ejection Fraction: A Fraction of the Whole.Antioxidants (Basel, Switzerland) · 2024Review
- Multi-omics association study of DNA methylation and gene expression levels and diagnoses of cardiovascular diseases in Danish Twins.Clinical epigenetics · 2024Article
- Broadening Horizons: Exploring mtDAMPs as a Mechanism and Potential Intervention Target in Cardiovascular Diseases.Aging and disease · 2023Review
- Article
- GPR19 Coordinates Multiple Molecular Aspects of Stress Responses Associated with the Aging Process.International journal of molecular sciences · 2023Article
- DNA damage response signaling: A common link between cancer and cardiovascular diseases.Cancer medicine · 2023Review
- Vascular aging and cardiovascular disease: pathophysiology and measurement in the coronary arteries.Frontiers in cardiovascular medicine · 2023Review
47 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
rationaleDNA damage is present in both genomic and mitochondrial DNA in atherosclerosis. However, whether DNA damage itself promotes atherosclerosis, or is simply a byproduct of the risk factors that promote atherosclerosis, is unknown.
objectiveTo examine the effect of DNA damage on atherosclerosis, we studied apolipoprotein (Apo)E(-/-) mice that were haploinsufficient for the protein kinase ATM (ataxia telangiectasia mutated), which coordinates DNA repair. METHODS AND
resultsATM(+/-)/ApoE(-/-) mice developed accelerated atherosclerosis and multiple features of the metabolic syndrome, including hypertension, hypercholesterolemia, obesity, steatohepatitis, and glucose intolerance. Transplantation with ATM(+/+) bone marrow attenuated atherosclerosis but not the metabolic syndrome. ATM(+/-) smooth muscle cells and macrophages showed increased nuclear DNA damage and defective DNA repair signaling, growth arrest, and apoptosis. Metabolomic screening of ATM(+/-)/ApoE(-/-) mouse tissues identified metabolic changes compatible with mitochondrial defects, with increased β-hydroxybutyrate but reduced lactate, reduced glucose, and alterations in multiple lipid species. ATM(+/-)/ApoE(-/-) mouse tissues showed an increased frequency of a mouse mitochondrial "common" deletion equivalent and reduced mitochondrial oxidative phosphorylation.
conclusionsWe propose that failure of DNA repair generates defects in cell proliferation, apoptosis, and mitochondrial dysfunction. This in turn leads to ketosis, hyperlipidemia, and increased fat storage, promoting atherosclerosis and the metabolic syndrome. Prevention of mitochondrial dysfunction may represent a novel target in cardiovascular disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.