Essential hypertension (EH) is a multifactorial disease of the cardiovascular system that is influenced by the interplay of genetic, epigenetic, and environmental factors. The molecular dynamics underlying EH etiopathogenesis is unknown; however, earlier studies have revealed EH-associated genetic variants. Nevertheless, this finding alone is not sufficient to explain the variability in blood pressure, suggesting that other risk factors are involved, such as epigenetic modifications. Therefore, this review highlights the potential contribution of well-defined epigenetic mechanisms in EH, specifically, DNA methylation, post-translational histone modifications, and microRNAs. We further emphasize global and gene-specific DNA methylation as one of the most well-studied hallmarks among all epigenetic modifications in EH. In addition, post-translational histone modifications, such as methylation, acetylation, and phosphorylation, are described as important epigenetic markers associated with EH. Finally, we discuss microRNAs that affect blood pressure by regulating master genes such as those implicated in the renin-angiotensin-aldosterone system. These epigenetic modifications, which appear to contribute to various cardiovascular diseases, including EH, may be a promising research area for the development of novel future strategies for EH prevention and therapeutics.
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EMU, LJM, and RCB were supported by AHA SFRN23680000 and NIH UL1 TR001425 (CTSA). MA was a postdoctoral fellowship recipient of the AHA SFRN23680000. SS was supported by NIH National Heart, Lung, and Blood grants, including R01HL130356 and R01HL105826, and the American Heart Association (AHA) Midwest Affiliate Research Programs, including Cardiovascular Genome-Phenome Study 15CVGPSD27020012 and Catalyst 17CCRG33671128.
Conflict of interest
SS provides consulting services to AstraZeneca and Amgen unrelated to the content of this manuscript. The remaining authors declare that they have no conflict of interest.
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Arif, M., Sadayappan, S., Becker, R.C. et al. Epigenetic modification: a regulatory mechanism in essential hypertension. Hypertens Res 42, 1099–1113 (2019). https://doi.org/10.1038/s41440-019-0248-0
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