Variability of Mitochondrial DNA Heteroplasmy: Association with Asymptomatic Carotid Atherosclerosis

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2024 Aug 29

PMID 39200332

Authors

Margarita A Sazonova

Tatiana V Kirichenko

Anastasia I Ryzhkova

Marina D Sazonova

Natalya A Doroschuk

Andrey V Omelchenko

Nikita G Nikiforov

Yulia I Ragino

Anton Yu Postnov

Affiliations

Soon will be listed here.

Abstract

Atherosclerosis is one of the main reasons for cardiovascular disease development. This study aimed to analyze the association of mtDNA mutations and atherosclerotic plaques in carotid arteries of patients with atherosclerosis and conditionally healthy study participants from the Novosibirsk region. PCR fragments of DNA containing the regions of 10 investigated mtDNA mutations were pyrosequenced. The heteroplasmy levels of mtDNA mutations were analyzed using a quantitative method based on pyrosequencing technology developed by M. A. Sazonova and colleagues. In the analysis of samples of patients with atherosclerotic plaques of the carotid arteries and conditionally healthy study participants from the Novosibirsk region, four proatherogenic mutations in the mitochondrial genome (m.5178C>A, m.652delG, m.12315G>A and m.3256C>T) and three antiatherogenic mutations in mtDNA (m.13513G>A, m.652insG, and m.14846G>A) were detected. A west-east gradient was found in the distribution of the mtDNA mutations m.5178C>A, m.3256C>T, m.652insG, and m.13513G>A. Therefore, four proatherogenic mutations in the mitochondrial genome (m.5178C>A, m.652delG, m.12315G>A, and m.3256C>T) and three antiatherogenic mutations in mtDNA (m.13513G>A, m.652insG, and m.14846G>A) were detected in patients with atherosclerotic plaques in their carotid arteries from the Novosibirsk region.

Citing Articles

The Role of mtDNA Mutations in Atherosclerosis: The Influence of Mitochondrial Dysfunction on Macrophage Polarization.

Fedotova E, Berezhnov A, Popov D, Shitikova E, Vinokurov A Int J Mol Sci. 2025; 26(3).

PMID: 39940788 PMC: 11817597. DOI: 10.3390/ijms26031019.

References

Battle S, Puiu D, Verlouw J, Broer L, Boerwinkle E, Taylor K . A bioinformatics pipeline for estimating mitochondrial DNA copy number and heteroplasmy levels from whole genome sequencing data. NAR Genom Bioinform. 2022; 4(2):lqac034. PMC: 9112767. DOI: 10.1093/nargab/lqac034. View

Lee S, Han J . Mitochondrial Mutations in Cardiac Disorders. Adv Exp Med Biol. 2017; 982:81-111. DOI: 10.1007/978-3-319-55330-6_5. View

Zhang T, Chen J, Tang X, Luo Q, Xu D, Yu B . Interaction between adipocytes and high-density lipoprotein:new insights into the mechanism of obesity-induced dyslipidemia and atherosclerosis. Lipids Health Dis. 2019; 18(1):223. PMC: 6913018. DOI: 10.1186/s12944-019-1170-9. View

Zhang H, Zeng Y, Yang H, Hu Y, Hu Y, Chen W . Familial factors, diet, and risk of cardiovascular disease: a cohort analysis of the UK Biobank. Am J Clin Nutr. 2021; 114(5):1837-1846. DOI: 10.1093/ajcn/nqab261. View

Doroschuk N, Postnov A, Doroschuk A, Ryzhkova A, Sinyov V, Sazonova M . An original biomarker for the risk of developing cardiovascular diseases and their complications: Telomere length. Toxicol Rep. 2021; 8:499-504. PMC: 7941069. DOI: 10.1016/j.toxrep.2021.02.024. View

Grady J, Pickett S, Ng Y, Alston C, Blakely E, Hardy S . mtDNA heteroplasmy level and copy number indicate disease burden in m.3243A>G mitochondrial disease. EMBO Mol Med. 2018; 10(6). PMC: 5991564. DOI: 10.15252/emmm.201708262. View

Touboul P, Hennerici M, Meairs S, Adams H, Amarenco P, Bornstein N . Mannheim carotid intima-media thickness and plaque consensus (2004-2006-2011). An update on behalf of the advisory board of the 3rd, 4th and 5th watching the risk symposia, at the 13th, 15th and 20th European Stroke Conferences, Mannheim, Germany,.... Cerebrovasc Dis. 2012; 34(4):290-6. PMC: 3760791. DOI: 10.1159/000343145. View

Akodad M, Sicard P, Fauconnier J, Roubille F . Colchicine and myocardial infarction: A review. Arch Cardiovasc Dis. 2020; 113(10):652-659. DOI: 10.1016/j.acvd.2020.04.007. View

Viering D, Vermeltfoort L, Bindels R, Deinum J, de Baaij J . Electrolyte Disorders in Mitochondrial Cytopathies: A Systematic Review. J Am Soc Nephrol. 2023; 34(11):1875-1888. PMC: 10631606. DOI: 10.1681/ASN.0000000000000224. View

10.

Chavan V, Willis J, Walker S, Clark H, Liu X, Fox M . Central presynaptic terminals are enriched in ATP but the majority lack mitochondria. PLoS One. 2015; 10(4):e0125185. PMC: 4416033. DOI: 10.1371/journal.pone.0125185. View

11.

Pereira C, Moraes C . Current strategies towards therapeutic manipulation of mtDNA heteroplasmy. Front Biosci (Landmark Ed). 2016; 22(6):991-1010. PMC: 6986768. DOI: 10.2741/4529. View

12.

Sazonova M, Ryzhkova A, Sinyov V, Galitsyna E, Melnichenko A, Demakova N . Mitochondrial Genome Mutations Associated with Myocardial Infarction. Dis Markers. 2018; 2018:9749457. PMC: 5835263. DOI: 10.1155/2018/9749457. View

13.

Snyder R, Kleeberger S . Role of Mitochondrial DNA in Inflammatory Airway Diseases. Compr Physiol. 2021; 11(2):1485-1499. DOI: 10.1002/cphy.c200010. View

14.

Sazonova M, Postnov A, Orekhov A, Sobenin I . [A new method of quantitative estimation of mutant allele in mitochondrial genome]. Patol Fiziol Eksp Ter. 2012; (4):81-4. View

15.

Dominic E, Ramezani A, Anker S, Verma M, Mehta N, Rao M . Mitochondrial cytopathies and cardiovascular disease. Heart. 2014; 100(8):611-8. DOI: 10.1136/heartjnl-2013-304657. View

16.

Frazier A, Compton A, Kishita Y, Hock D, Welch A, Amarasekera S . Fatal perinatal mitochondrial cardiac failure caused by recurrent duplications in the locus. Med. 2021; 2(1):49-73. PMC: 7875323. DOI: 10.1016/j.medj.2020.06.004. View

17.

Carlton J, Jones H, Eggert U . Membrane and organelle dynamics during cell division. Nat Rev Mol Cell Biol. 2020; 21(3):151-166. DOI: 10.1038/s41580-019-0208-1. View

18.

Pinti M, Fink G, Hathaway Q, Durr A, Kunovac A, Hollander J . Mitochondrial dysfunction in type 2 diabetes mellitus: an organ-based analysis. Am J Physiol Endocrinol Metab. 2019; 316(2):E268-E285. PMC: 6397358. DOI: 10.1152/ajpendo.00314.2018. View

19.

Dominic A, Banerjee P, Hamilton D, Le N, Abe J . Time-dependent replicative senescence vs. disturbed flow-induced pre-mature aging in atherosclerosis. Redox Biol. 2020; 37:101614. PMC: 7767754. DOI: 10.1016/j.redox.2020.101614. View

20.

Sazonova M, Sinyov V, Barinova V, Ryzhkova A, Bobryshev Y, Orekhov A . Association of mitochondrial mutations with the age of patients having atherosclerotic lesions. Exp Mol Pathol. 2015; 99(3):717-9. DOI: 10.1016/j.yexmp.2015.11.019. View