The Role of DNMT and HDACs in the Fetal Programming of Hypertension by Glucocorticoids
The causes of hypertension are complex and involve both genetic and environmental factors. Environment changes during fetal development have been linked to adult diseases including hypertension. Studies show that timed in utero exposure to the synthetic glucocorticoid (GC) dexamethasone (Dex) result...
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doaj-dc8a6807b1ec44a88a91c7fadafe566c2020-11-25T02:26:47ZengHindawi LimitedOxidative Medicine and Cellular Longevity1942-09001942-09942020-01-01202010.1155/2020/57517685751768The Role of DNMT and HDACs in the Fetal Programming of Hypertension by GlucocorticoidsJ. Lamothe0S. Khurana1S. Tharmalingam2C. Williamson3C. J. Byrne4N. Khaper5S. Mercier6T. C. Tai7Biomolecular Sciences, Laurentian University, Sudbury, ON, CanadaMedical Science Division, Northern Ontario School of Medicine Sudbury, ON, CanadaMedical Science Division, Northern Ontario School of Medicine Sudbury, ON, CanadaBiology, Laurentian University, Sudbury, ON, CanadaBiology, Laurentian University, Sudbury, ON, CanadaMedical Science Division, Northern Ontario School of Medicine Thunder Bay, ON, CanadaSchool of Human Kinetics, Laurentian University, Sudbury, ON, CanadaBiomolecular Sciences, Laurentian University, Sudbury, ON, CanadaThe causes of hypertension are complex and involve both genetic and environmental factors. Environment changes during fetal development have been linked to adult diseases including hypertension. Studies show that timed in utero exposure to the synthetic glucocorticoid (GC) dexamethasone (Dex) results in the development of hypertension in adult rats. Evidence suggests that in utero stress can alter patterns of gene expression, possibly a result of alterations in the topology of the genome by epigenetic markers such as DNA methyltransferases (DNMTs) and histone deacetylases (HDACs). The objective of this study was to determine the effects of epigenetic regulators in the fetal programming and the development of adult hypertension. Specifically, this research examined the effects of the HDAC inhibitor valproic acid (VPA) and the DNMT inhibitor 5-aza-2′-deoxycytidine (5aza2DC) on blood pressure (BP) and gene expression in prenatal Dex-programmed rats. Data suggest that both VPA and 5aza2DC attenuated the Dex-mediated development of hypertension and restored BP to control levels. Epigenetic DNMT inhibition (DNMTi) or HDAC inhibition (HDACi) also successfully attenuated elevations in the majority of altered catecholamine (CA) enzyme expression, phenylethanolamine N-methyltransferase (PNMT) protein, and elevated epinephrine (Epi) levels in males. Although females responded to HDACi similar to males, DNMTi drove increased glucocorticoid receptor (GR) and PNMT expression and elevations in circulating Epi in females despite showing normotensive BP.http://dx.doi.org/10.1155/2020/5751768 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
J. Lamothe S. Khurana S. Tharmalingam C. Williamson C. J. Byrne N. Khaper S. Mercier T. C. Tai |
spellingShingle |
J. Lamothe S. Khurana S. Tharmalingam C. Williamson C. J. Byrne N. Khaper S. Mercier T. C. Tai The Role of DNMT and HDACs in the Fetal Programming of Hypertension by Glucocorticoids Oxidative Medicine and Cellular Longevity |
author_facet |
J. Lamothe S. Khurana S. Tharmalingam C. Williamson C. J. Byrne N. Khaper S. Mercier T. C. Tai |
author_sort |
J. Lamothe |
title |
The Role of DNMT and HDACs in the Fetal Programming of Hypertension by Glucocorticoids |
title_short |
The Role of DNMT and HDACs in the Fetal Programming of Hypertension by Glucocorticoids |
title_full |
The Role of DNMT and HDACs in the Fetal Programming of Hypertension by Glucocorticoids |
title_fullStr |
The Role of DNMT and HDACs in the Fetal Programming of Hypertension by Glucocorticoids |
title_full_unstemmed |
The Role of DNMT and HDACs in the Fetal Programming of Hypertension by Glucocorticoids |
title_sort |
role of dnmt and hdacs in the fetal programming of hypertension by glucocorticoids |
publisher |
Hindawi Limited |
series |
Oxidative Medicine and Cellular Longevity |
issn |
1942-0900 1942-0994 |
publishDate |
2020-01-01 |
description |
The causes of hypertension are complex and involve both genetic and environmental factors. Environment changes during fetal development have been linked to adult diseases including hypertension. Studies show that timed in utero exposure to the synthetic glucocorticoid (GC) dexamethasone (Dex) results in the development of hypertension in adult rats. Evidence suggests that in utero stress can alter patterns of gene expression, possibly a result of alterations in the topology of the genome by epigenetic markers such as DNA methyltransferases (DNMTs) and histone deacetylases (HDACs). The objective of this study was to determine the effects of epigenetic regulators in the fetal programming and the development of adult hypertension. Specifically, this research examined the effects of the HDAC inhibitor valproic acid (VPA) and the DNMT inhibitor 5-aza-2′-deoxycytidine (5aza2DC) on blood pressure (BP) and gene expression in prenatal Dex-programmed rats. Data suggest that both VPA and 5aza2DC attenuated the Dex-mediated development of hypertension and restored BP to control levels. Epigenetic DNMT inhibition (DNMTi) or HDAC inhibition (HDACi) also successfully attenuated elevations in the majority of altered catecholamine (CA) enzyme expression, phenylethanolamine N-methyltransferase (PNMT) protein, and elevated epinephrine (Epi) levels in males. Although females responded to HDACi similar to males, DNMTi drove increased glucocorticoid receptor (GR) and PNMT expression and elevations in circulating Epi in females despite showing normotensive BP. |
url |
http://dx.doi.org/10.1155/2020/5751768 |
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