Dietary Sodium Restriction Results in Tissue-Specific Changes in DNA Methylation in Humans

Dietary sodium affects blood pressure (BP) and vascular function. Animal studies suggest epigenetic changes (eg, DNA methylation) are involved. We hypothesized that sodium restriction induces methylation changes in T cells and arterioles in humans. Fifty subjects (49% women) were placed on 1200-mg s...

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Published inHypertension (Dallas, Tex. 1979) Vol. 78; no. 2; pp. 434 - 446
Main Authors Kidambi, Srividya, Pan, Xiaoqing, Yang, Chun, Liu, Pengyuan, Roberts, Michelle L., Li, Yingchuan, Wang, Tao, Laud, Purushottam W., Liu, Yi, Rubens, Merrill, Thomas, Richard, Widlansky, Michael E., Beyer, Andreas M., Liu, Yong, Cowley, Allen W., Kotchen, Theodore A., Munyura, Yannick, Moosreiner, Andrea, Mattson, David L., Liang, Mingyu
Format Journal Article
LanguageEnglish
Published United States Lippincott Williams & Wilkins 01.08.2021
Subjects
Adult
Aged
Arterioles - metabolism
Blood Pressure - physiology
Diet, Sodium-Restricted
DNA Methylation
Epigenomics
Female
Humans
Male
Middle Aged
Sodium Chloride, Dietary
T-Lymphocytes - metabolism
DNA methylation
blood pressure
sodium
epigenomics
gene expression
Online AccessGet full text
ISSN0194-911X
1524-4563
1524-4563
DOI10.1161/HYPERTENSIONAHA.120.17351

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Abstract Dietary sodium affects blood pressure (BP) and vascular function. Animal studies suggest epigenetic changes (eg, DNA methylation) are involved. We hypothesized that sodium restriction induces methylation changes in T cells and arterioles in humans. Fifty subjects (49% women) were placed on 1200-mg sodium/day diet for 2 weeks. BP and brachial artery flow-mediated dilation were evaluated. Methylation sequencing (pre- and post-diet) was performed on T-cell (n=50) and biopsied arteriolar (n=10) DNA. RNA sequencing was also performed on arterioles (n=11). Over 2 weeks, mean sodium consumption was 946 mg/day. Average BP reductions after low-sodium intake were −8±13/−4±9 mm Hg (P<0.001). Flow-mediated dilation improved (5.8±2.9% to 6.8±3.4%; P=0.03). T-cell DNA was substantially more methylated than arterioles. The differentially methylated regions (false discovery rate, <0.05) identified in T cells and arterioles after sodium restriction were located in 117 and 71 genes, respectively. Four genes were identified in both T cells and arterioles (P=0.009 for the overlap). The dietary effects on methylation in several DNA regions were associated with dietary effects on BP. Several differentially expressed genes in arterioles contained differentially methylated regions at the significance level of P<0.05. In addition, 46 genes contained differentially methylated regions in both human and SS/Mcw rat T cells (P=0.03 for the overlap). Sodium restriction significantly affected DNA methylation in T cells and arterioles, some of which are associated with BP. Methylation patterns and sodium effects on methylation are largely tissue specific but also have overlaps between tissues and species. These findings may lead to better understanding of dietary sodium interactions with cellular processes and, therefore, novel therapeutic targets.
AbstractList [Figure: see text].[Figure: see text].
Dietary sodium affects blood pressure (BP) and vascular function. Animal studies suggest epigenetic changes (eg, DNA methylation) are involved. We hypothesized that sodium restriction induces methylation changes in T cells and arterioles in humans. Fifty subjects (49% women) were placed on 1200-mg sodium/day diet for 2 weeks. BP and brachial artery flow-mediated dilation were evaluated. Methylation sequencing (pre- and post-diet) was performed on T-cell (n=50) and biopsied arteriolar (n=10) DNA. RNA sequencing was also performed on arterioles (n=11). Over 2 weeks, mean sodium consumption was 946 mg/day. Average BP reductions after low-sodium intake were −8±13/−4±9 mm Hg (P<0.001). Flow-mediated dilation improved (5.8±2.9% to 6.8±3.4%; P=0.03). T-cell DNA was substantially more methylated than arterioles. The differentially methylated regions (false discovery rate, <0.05) identified in T cells and arterioles after sodium restriction were located in 117 and 71 genes, respectively. Four genes were identified in both T cells and arterioles (P=0.009 for the overlap). The dietary effects on methylation in several DNA regions were associated with dietary effects on BP. Several differentially expressed genes in arterioles contained differentially methylated regions at the significance level of P<0.05. In addition, 46 genes contained differentially methylated regions in both human and SS/Mcw rat T cells (P=0.03 for the overlap). Sodium restriction significantly affected DNA methylation in T cells and arterioles, some of which are associated with BP. Methylation patterns and sodium effects on methylation are largely tissue specific but also have overlaps between tissues and species. These findings may lead to better understanding of dietary sodium interactions with cellular processes and, therefore, novel therapeutic targets.
Dietary sodium affects blood pressure (BP) and vascular function. Animal studies suggest epigenetic changes (eg, DNA methylation) are involved. We hypothesized that sodium restriction induces methylation changes in T cells and arterioles in humans. Fifty subjects (49% women) were placed on 1200-mg sodium/day diet for 2 weeks. BP and brachial artery flow-mediated dilation were evaluated. Methylation sequencing (pre- and post-diet) was performed on T-cell (n=50) and biopsied arteriolar (n=10) DNA. RNA sequencing was also performed on arterioles (n=11). Over 2 weeks, mean sodium consumption was 946 mg/day. Average BP reductions after low-sodium intake were −8±13/−4±9 mm Hg ( P <0.001). Flow-mediated dilation improved (5.8±2.9% to 6.8±3.4%; P =0.03). T-cell DNA was substantially more methylated than arterioles. The differentially methylated regions (false discovery rate, <0.05) identified in T cells and arterioles after sodium restriction were located in 117 and 71 genes, respectively. Four genes were identified in both T cells and arterioles ( P =0.009 for the overlap). The dietary effects on methylation in several DNA regions were associated with dietary effects on BP. Several differentially expressed genes in arterioles contained differentially methylated regions at the significance level of P <0.05. In addition, 46 genes contained differentially methylated regions in both human and SS/Mcw rat T cells ( P =0.03 for the overlap). Sodium restriction significantly affected DNA methylation in T cells and arterioles, some of which are associated with BP. Methylation patterns and sodium effects on methylation are largely tissue specific but also have overlaps between tissues and species. These findings may lead to better understanding of dietary sodium interactions with cellular processes and, therefore, novel therapeutic targets.
[Figure: see text].
Author Kotchen, Theodore A.
Pan, Xiaoqing
Liu, Pengyuan
Yang, Chun
Wang, Tao
Widlansky, Michael E.
Beyer, Andreas M.
Cowley, Allen W.
Moosreiner, Andrea
Rubens, Merrill
Thomas, Richard
Roberts, Michelle L.
Liu, Yi
Li, Yingchuan
Mattson, David L.
Liu, Yong
Kidambi, Srividya
Munyura, Yannick
Laud, Purushottam W.
Liang, Mingyu
AuthorAffiliation Division of Endocrinology, Department of Medicine (S.K., M.R., R.T., T.A.K., Y.M.), Medical College of Wisconsin, Milwaukee
Division of Cardiovascular Disease, Department of Medicine (M.E.W., A.M.B.), Medical College of Wisconsin, Milwaukee
Department of Physiology, Center of Systems Molecular Medicine (X.P., C.Y., P.L., M.L.R., Y. Li, A.M.B., Yong Liu, A.W.C., D.L.M., M.L.), Medical College of Wisconsin, Milwaukee
Clinical and Translational Science Institute (A.M.), Medical College of Wisconsin, Milwaukee
Division of Biostatistics, Institute for Health and Equity (T.W., P.W.L.), Medical College of Wisconsin, Milwaukee
Sir Run Run Shaw Hospital, Institute of Translational Medicine, Zhejiang University, China (P.L., Yi Liu)
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Issue 2
Keywords DNA methylation
blood pressure
sodium
epigenomics
gene expression
Language English
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Author contribution
SK, TAK, and ML designed and led the study. SK, XP, TAK, and ML drafted the manuscript. XP and PL analyzed the methylation data. XP, PL, TW, PWL and ML developed or performed the statistical analysis. Y Li, MLR, and CY performed library preparation for sequencing. Y Li, Y Liu, AWC, and DLM contributed to study design and development. SK, MR, RT, MEW, AMB, TAK, YM, and AM collected and analyzed clinical and phenotypic data. All authors edited or approved the article.
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PublicationDateYYYYMMDD 2021-08-01
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  year: 2021
  text: 2021-August-01
  day: 01
PublicationDecade 2020
PublicationPlace United States
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PublicationTitle Hypertension (Dallas, Tex. 1979)
PublicationTitleAlternate Hypertension
PublicationYear 2021
Publisher Lippincott Williams & Wilkins
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Snippet Dietary sodium affects blood pressure (BP) and vascular function. Animal studies suggest epigenetic changes (eg, DNA methylation) are involved. We hypothesized...
[Figure: see text].
[Figure: see text].[Figure: see text].
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StartPage 434
SubjectTerms Adult
Aged
Arterioles - metabolism
Blood Pressure - physiology
Diet, Sodium-Restricted
DNA Methylation
Epigenomics
Female
Humans
Male
Middle Aged
Sodium Chloride, Dietary
T-Lymphocytes - metabolism
Title Dietary Sodium Restriction Results in Tissue-Specific Changes in DNA Methylation in Humans
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https://www.ncbi.nlm.nih.gov/pubmed/34120454
https://www.proquest.com/docview/2540719998
https://pubmed.ncbi.nlm.nih.gov/PMC9299531
Volume 78
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