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Mitochondria-targeted Uncouplers Decrease Inflammatory Reactions in Endothelial Cells by Enhancing Methylation of the
Liudmila A Zinovkina1, Ciara I Makievskaya1,2, Ivan I Galkin3,4
1Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119991 Moscow, Russia.
Current Molecular Pharmacology
|August 17, 2023
Summary
Mild mitochondrial uncouplers increase ICAM1 gene promoter methylation, reducing inflammation. This epigenetic change in endothelial cells offers potential therapeutic strategies for cardiovascular diseases.
Area of Science:
- Cell Biology
- Epigenetics
- Mitochondrial Biology
Background:
- Endothelial inflammation drives cardiovascular diseases.
- Mitochondria regulate endothelial cell function.
- Mild mitochondrial uncoupling shows anti-inflammatory effects, but mechanisms are unclear.
Purpose of the Study:
- Investigate mitochondrial uncouplers' effects on endothelial ICAM1 gene promoter methylation.
- Explore the epigenetic mechanisms behind the anti-inflammatory activity of mitochondrial uncouplers.
Main Methods:
- Studied mitochondria-targeted uncouplers: SkQ1, C12TPP, and DNP.
- Measured intercellular adhesion molecule 1 (ICAM1) mRNA expression via RT-qPCR.
- Assessed ICAM1 promoter CpG site methylation using bisulfite sequencing.
Main Results:
- DNP and C12TPP decreased ICAM1 expression.
- This downregulation correlated with increased ICAM1 promoter CpG methylation.
- No significant changes in intracellular or intramitochondrial ATP levels were observed.
Conclusions:
- Mitochondrial uncouplers enhance ICAM1 promoter methylation, reducing ICAM1 mRNA levels.
- Epigenetic modification of the ICAM1 promoter may mediate the anti-inflammatory effects of mitochondrial uncoupling.
- Mitochondrial uncouplers show therapeutic potential for endothelial inflammation via DNA methylation changes.
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