Faculty Collaboration Database

Epigenetic Modifications in T Cells: The Role of DNA Methylation in Salt-Sensitive Hypertension. Hypertension 2020 Feb;75(2):372-382

Date

12/17/2019

Pubmed ID

31838911

Pubmed Central ID

PMC7058976

DOI

10.1161/HYPERTENSIONAHA.119.13716

Scopus ID

2-s2.0-85077761000 (requires institutional sign-in at Scopus site)   26 Citations

Abstract

The SS (Dahl salt sensitive) rat is an established model of hypertension and renal damage that is accompanied with immune system activation in response to a high-salt diet. Investigations into the effects of sodium-independent and dependent components of the diet were shown to affect the disease phenotype with SS/MCW (JrHsdMcwi) rats maintained on a purified diet (AIN-76A) presenting with a more severe phenotype relative to grain-fed SS/CRL (JrHsdMcwiCrl) rats. Since contributions of the immune system, environment, and diet are documented to alter this phenotype, this present study examined the epigenetic profile of T cells isolated from the periphery and the kidney from these colonies. T cells isolated from kidneys of the 2 colonies revealed that transcriptomic and functional differences may contribute to the susceptibility of hypertension and renal damage. In response to high-salt challenge, the methylome of T cells isolated from the kidney of SS/MCW exhibit a significant increase in differentially methylated regions with a preference for hypermethylation compared with the SS/CRL kidney T cells. Circulating T cells exhibited similar methylation profiles between colonies. Utilizing transcriptomic data from T cells isolated from the same animals upon which the DNA methylation analysis was performed, a predominant negative correlation was observed between gene expression and DNA methylation in all groups. Lastly, inhibition of DNA methyltransferases blunted salt-induced hypertension and renal damage in the SS/MCW rats providing a functional role for methylation. This study demonstrated the influence of epigenetic modifications to immune cell function, highlighting the need for further investigations.

Author List

Dasinger JH, Alsheikh AJ, Abais-Battad JM, Pan X, Fehrenbach DJ, Lund H, Roberts ML, Cowley AW Jr, Kidambi S, Kotchen TA, Liu P, Liang M, Mattson DL

Authors

Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of Wisconsin
Srividya Kidambi MD Sr Medical Director, Chief, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Blood Pressure
DNA Methylation
Disease Models, Animal
Epigenesis, Genetic
Hypertension
Male
Phenotype
Rats
Rats, Inbred Dahl
Sodium Chloride, Dietary
T-Lymphocytes