Mitochondrial DNA Methylation Is Higher in Acute Coronary Syndrome Than in Stable Coronary Artery Disease

Overview

Journal In Vivo

Specialty Oncology

Date 2021 Jan 6

PMID 33402465

Citations 7

Authors

Sang Hyun Park

Soo Young Lee

Soon Ae Kim

Affiliations

Soon will be listed here.

Abstract

Background/aim: Decreased mitochondrial DNA copy number (mtDNA-CN) has been associated with coronary artery disease (CAD). We aimed to clarify the difference between stable CAD (SCAD) and acute coronary syndrome (ACS) regarding mtDNA-CN and the DNA methylation ratio in regions influencing the regulation of mitochondrial biogenesis.

Materials And Methods: Using quantitative real-time polymerase chain reaction, mtDNA-CN was measured in peripheral blood leukocytes sampled from 50 patients with SCAD and 50 with ACS. We then conducted bisulfite modification of DNA followed by methylation-specific polymerase chain reaction to quantify mtDNA methylation in the mitochondrial D-loop region (mtDLR) and nuclear DNA methylation in the promoter region of nuclear peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) gene.

Results: Compared to patients with SCAD, those with ACS had significantly lower relative mtDNA-CN (0.89±0.24 vs. 1.00±0.28, p=0.013) and higher DNA methylation ratio of the mtDLR (1.11±0.24 vs. 1.00±0.25, p=0.027) Conclusion: Our findings suggest that increased DNA methylation in the mtDLR, which translates into reduced mtDNA content, may affect the clinical phenotype of CAD.

Citing Articles

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References

Ballinger S, Patterson C, Burow D, Conklin C, Hu Z, Reuf J . Mitochondrial integrity and function in atherogenesis. Circulation. 2002; 106(5):544-9. DOI: 10.1161/01.cir.0000023921.93743.89. View

Dzitoyeva S, Chen H, Manev H . Effect of aging on 5-hydroxymethylcytosine in brain mitochondria. Neurobiol Aging. 2012; 33(12):2881-91. PMC: 3462297. DOI: 10.1016/j.neurobiolaging.2012.02.006. View

Robin E, Wong R . Mitochondrial DNA molecules and virtual number of mitochondria per cell in mammalian cells. J Cell Physiol. 1988; 136(3):507-13. DOI: 10.1002/jcp.1041360316. View

Infantino V, Castegna A, Iacobazzi F, Spera I, Scala I, Andria G . Impairment of methyl cycle affects mitochondrial methyl availability and glutathione level in Down's syndrome. Mol Genet Metab. 2011; 102(3):378-82. DOI: 10.1016/j.ymgme.2010.11.166. View

Hamm C, Ravkilde J, Gerhardt W, Jorgensen P, Peheim E, Ljungdahl L . The prognostic value of serum troponin T in unstable angina. N Engl J Med. 1992; 327(3):146-50. DOI: 10.1056/NEJM199207163270302. View

Ghivizzani S, Madsen C, Nelen M, Ammini C, Hauswirth W . In organello footprint analysis of human mitochondrial DNA: human mitochondrial transcription factor A interactions at the origin of replication. Mol Cell Biol. 1994; 14(12):7717-30. PMC: 359313. DOI: 10.1128/mcb.14.12.7717-7730.1994. View

Baccarelli A, Byun H . Platelet mitochondrial DNA methylation: a potential new marker of cardiovascular disease. Clin Epigenetics. 2015; 7:44. PMC: 4404685. DOI: 10.1186/s13148-015-0078-0. View

Pirola C, Fernandez Gianotti T, Burgueno A, Rey-Funes M, Loidl C, Mallardi P . Epigenetic modification of liver mitochondrial DNA is associated with histological severity of nonalcoholic fatty liver disease. Gut. 2012; 62(9):1356-63. DOI: 10.1136/gutjnl-2012-302962. View

Wallace D, Fan W . Energetics, epigenetics, mitochondrial genetics. Mitochondrion. 2009; 10(1):12-31. PMC: 3245717. DOI: 10.1016/j.mito.2009.09.006. View

10.

Byun H, Panni T, Motta V, Hou L, Nordio F, Apostoli P . Effects of airborne pollutants on mitochondrial DNA methylation. Part Fibre Toxicol. 2013; 10:18. PMC: 3660297. DOI: 10.1186/1743-8977-10-18. View

11.

Sookoian S, Rosselli M, Gemma C, Burgueno A, Fernandez Gianotti T, Castano G . Epigenetic regulation of insulin resistance in nonalcoholic fatty liver disease: impact of liver methylation of the peroxisome proliferator-activated receptor γ coactivator 1α promoter. Hepatology. 2010; 52(6):1992-2000. DOI: 10.1002/hep.23927. View

12.

Park G, An H, Lee S, Cho Y, Gil E, Her S . Impact of Metabolic Syndrome on Subclinical Atherosclerosis in Asymptomatic Individuals. Circ J. 2015; 79(8):1799-806. DOI: 10.1253/circj.CJ-14-1197. View

13.

Chen S, Xie X, Wang Y, Gao Y, Xie X, Yang J . Association between leukocyte mitochondrial DNA content and risk of coronary heart disease: a case-control study. Atherosclerosis. 2014; 237(1):220-6. DOI: 10.1016/j.atherosclerosis.2014.08.051. View

14.

Jeng J, Yeh T, Lee J, Lin S, Fong T, Hsieh R . Maintenance of mitochondrial DNA copy number and expression are essential for preservation of mitochondrial function and cell growth. J Cell Biochem. 2007; 103(2):347-57. DOI: 10.1002/jcb.21625. View

15.

Yoo H, Park M, Kim S . Difference in mitochondrial DNA copy number in peripheral blood cells between probands with autism spectrum disorders and their unaffected siblings. World J Biol Psychiatry. 2016; 18(2):151-156. DOI: 10.1080/15622975.2016.1234069. View

16.

Feng S, Xiong L, Ji Z, Cheng W, Yang H . Correlation between increased ND2 expression and demethylated displacement loop of mtDNA in colorectal cancer. Mol Med Rep. 2012; 6(1):125-30. DOI: 10.3892/mmr.2012.870. View

17.

Byun H, Baccarelli A . Environmental exposure and mitochondrial epigenetics: study design and analytical challenges. Hum Genet. 2014; 133(3):247-57. PMC: 4351743. DOI: 10.1007/s00439-013-1417-x. View

18.

Yu E, Calvert P, Mercer J, Harrison J, Baker L, Figg N . Mitochondrial DNA damage can promote atherosclerosis independently of reactive oxygen species through effects on smooth muscle cells and monocytes and correlates with higher-risk plaques in humans. Circulation. 2013; 128(7):702-12. DOI: 10.1161/CIRCULATIONAHA.113.002271. View

19.

Bacalini M, DAquila P, Marasco E, Nardini C, Montesanto A, Franceschi C . The methylation of nuclear and mitochondrial DNA in ageing phenotypes and longevity. Mech Ageing Dev. 2017; 165(Pt B):156-161. DOI: 10.1016/j.mad.2017.01.006. View

20.

Zheng L, Linarelli L, Liu L, Wall S, Greenawald M, Seidel R . Insulin resistance is associated with epigenetic and genetic regulation of mitochondrial DNA in obese humans. Clin Epigenetics. 2015; 7:60. PMC: 4479353. DOI: 10.1186/s13148-015-0093-1. View