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Updated: Jul 25, 2025
Methodology for Accurate Detection of Mitochondrial DNA Methylation
Published on: May 20, 2018
CABG Patients Develop Global DNA Hypermethylation, That Negatively Affect the Mitochondrial Function and Promote
Sri Rahavi Boovarahan1, Suresh Babu Kale2, Priyanka N Prem1
1Vascular Biology Laboratory, SASTRA Deemed University, Thanjavur 613401, India.
Abstract:
Global DNA hypermethylation and mitochondrial dysfunction are reported to be associated with the development of mild cognitive decline (MCI). The present study aims to generate preliminary data that connect the above association with post-surgical coronary artery bypass grafting (CABG) cognitive decline in patients. Data were collected from 70 CABG patients and 25 age-matched controls. Cognitive function was assessed using the Montreal Cognitive Assessment (MOCA) test on day 1 (before surgery) and on the day of discharge. Similarly, blood was collected before and one day after the CABG procedure for mitochondrial functional analysis and expression of DNA methylation genes. Test analysis score suggested 31 (44%) patients had MCI before discharge. These patients showed a significant decrease in complex I activity and an increase in malondialdehyde levels (p < 0.001) from the control blood samples. Post-surgical samples showed a significant reduction in blood MT-ND1 mRNA expression from control and from pre-surgical samples (p < 0.005), along with elevated DNMT1 gene expression (p < 0.047), with an insignificant increase in TET1 and TET3 gene expression. Correlation analysis showed a significant positive relation between cognitive decline and elevated blood DNMT1 and declined blood complex I activity, signifying that cognitive decline experienced by post-surgical CABG patients is associated with increased DNMT1 expression and declined complex I activity. Based on the data, we conclude that both DNA hypermethylation and mitochondrial dysfunction are associated with post-CABG MCI, where the former is negatively correlated, and the latter is positively correlated with post-surgical MCI in CABG cases. Additionally, a multimarker approach that comprises MOCA, DNA methylation, DNMT, and NQR activities can be utilized to stratify the population that is sensitive to developing post-CABG MCI.
Insights
Mild cognitive decline after coronary artery bypass grafting (CABG) is linked to DNA hypermethylation and mitochondrial dysfunction. These factors, along with specific gene expressions, can help identify patients at risk for post-surgical cognitive impairment.
Area of Science:
- Biochemistry
- Neuroscience
- Cardiovascular Surgery
Background:
- Global DNA hypermethylation and mitochondrial dysfunction are implicated in mild cognitive decline (MCI).
- Coronary artery bypass grafting (CABG) surgery is associated with post-operative cognitive dysfunction.
Purpose of the Study:
- To investigate the association between DNA methylation, mitochondrial dysfunction, and cognitive decline in patients undergoing CABG.
- To generate preliminary data linking pre-existing MCI mechanisms to post-CABG cognitive impairment.
Main Methods:
- Cognitive function was assessed using the Montreal Cognitive Assessment (MOCA) test before and after CABG in 70 patients and 25 controls.
- Blood samples were analyzed for mitochondrial function (Complex I activity, malondialdehyde) and DNA methylation gene expression (DNMT1, TET1, TET3, MT-ND1 mRNA) pre- and post-surgery.
Main Results:
- 44% of CABG patients exhibited MCI post-discharge.
- MCI patients showed decreased Complex I activity and increased malondialdehyde.
- Post-surgery, reduced MT-ND1 mRNA and elevated DNMT1 expression were observed, correlating with cognitive decline.
Conclusions:
- DNA hypermethylation and mitochondrial dysfunction are associated with post-CABG MCI.
- Elevated DNMT1 expression and decreased Complex I activity are linked to post-surgical cognitive decline.
- A multimarker approach (MOCA, DNA methylation, DNMT, NQR) may help stratify patients sensitive to post-CABG MCI.
