Abstract
BackgroundPlatelets are critical in the etiology of cardiovascular disease (CVD), and the mitochondria in these cells serve as an energy source for platelet function. Epigenetic factors, especially DNA methylation, have been employed as markers of CVD. Unlike nuclear DNA methylation, mitochondrial DNA (mtDNA) methylation has not been widely studied, in part, due to debate about its existence and role. In this study, we examined platelet mtDNA methylation in relation to CVD.ResultsWe measured mtDNA methylation in platelets by bisulfite-PCR pyrosequencing and examined associations of CVD with methylation in mitochondrial genes; cytochrome c oxidase (MT-CO1, MT-CO2, and MT-CO3); tRNA leucine 1 (MT-TL1); ATP synthase (MT-ATP6 and MT-ATP8); and NADH dehydrogenase (MT-MD5). We report that CVD patients have significantly higher mtDNA methylation than healthy controls in MT-CO1 (18.53%, P < 0.0001), MT-CO2 (3.33%, P = 0.0001), MT-CO3 (0.92%, P < 0.0001), and MT-TL1 (1.67%, P = 0.0001), which are involved in ATP synthesis. Platelet mtDNA methylation was not related with age, BMI, and race in this study.ConclusionsOur results suggest that platelet mtDNA methylation, which could serve as non-invasive and easy-to-obtain markers, may be implicated in the etiology of CVD.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-015-0078-0) contains supplementary material, which is available to authorized users.
Highlights
Platelets are critical in the etiology of cardiovascular disease (CVD), and the mitochondria in these cells serve as an energy source for platelet function
As CVD patients exhibit changes in the counts and proportions of individual leukocyte subtypes, as well as in the numbers of different cell types in the heart and blood vessels, differences in DNA methylation observed in these composite tissue types that are associated with CVD have been suggested to result solely from differences in cell type composition rather than from bona fide epigenetic changes
We observed a significant increase in mitochondrial DNA (mtDNA) methylation of all three MT-CO subunits in platelets from CVD patients
Summary
Platelets are critical in the etiology of cardiovascular disease (CVD), and the mitochondria in these cells serve as an energy source for platelet function. Unlike nuclear DNA methylation, mitochondrial DNA (mtDNA) methylation has not been widely studied, in part, due to debate about its existence and role. We examined platelet mtDNA methylation in relation to CVD. Platelets play an important role in CVD, both in the pathogenesis of atherosclerosis and in the development of acute thrombotic events. Mitochondrial DNA (mtDNA), as with nuclear DNA, can be methylated by machinery existing inside of the mitochondria [10,11,12] and can mediate the control of mitochondrial gene expression [13].
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