Research Paper Volume 12, Issue 7 pp 6276—6291

DNA N6-methyladenine modification in hypertension

Ye Guo 1, , Yuqing Pei 2, , Kexin Li 2, , Wei Cui 2, , Donghong Zhang 3, ,

  • 1 Department of Laboratory Medicine, Peking Union Medical College Hospital and Peking Union Medical College, Beijing 100021, PR China
  • 2 State Key Laboratory of Molecular Oncology, Department of Clinical Laboratory, National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, PR China
  • 3 Center for Molecular and Translational Medicine, Georgia State University, Research Science Center, Atlanta, GA 30303, USA

received: December 11, 2019 ; accepted: March 2, 2020 ; published: April 13, 2020 ;

https://doi.org/10.18632/aging.103023
How to Cite

Copyright © 2020 Guo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

DNA methylation has a role in the pathogenesis of essential hypertension. DNA N6-methyladenine (6mA) modification as a novel adenine methylation exists in human tissues, but whether it plays a role in hypertension development remains unclear. Here, we reported that the global 6mA DNA level in leukocytes was significantly reduced in patients with hypertension and was reversed with successful treatment. Age, systolic blood pressure, and serum total cholesterol and high-density lipoprotein levels were associated with decreased leukocyte 6mA DNA level. Elevated ALKBH1 (AlkB homolog 1), a demethylase of 6mA, level mediated this dynamic change in 6mA level in leukocytes and vascular smooth muscle cells in hypertension mouse and rat models. Knockdown of ALKBH1 suppressed angiotensin II-induced vascular smooth muscle phenotype transformation, proliferation and migration. ALKBH1-6mA directly and negatively regulated hypoxia inducible factor 1 α (HIF1α), which responded to angiotensin II-induced vascular remodeling. Collectively, our results demonstrate a potential epigenetic role for ALKBH1-6mA regulation in hypertension development, diagnosis and treatment.

Abbreviations

6mA: N6-methyl-2’-deoxyadenosine; N6AMT1: N6-adenine-specific DNA methyltransferase 1; ALKBH1: AlkB homolog 1; Ang II: Angiotensin II; VSMCs: Vascular smooth muscle cells; HIF1α: Hypoxia inducible factor 1α.