About this item:

253 Views | 404 Downloads

Author Notes:

Correspondence: Hanjoong Jo, Ph.D., John and Jan Portman Professor, Coulter Department of Biomedical Engineering, Georgia Tech and Emory University, 1760 Haygood Drive, Health Sciences Research Bldg E170, Atlanta, GA 30322.

Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.


Research Funding:

This work was supported by funding from National Institutes of Health grants HL119798, HL113451, HL095070 and HL124879 to HJ.

HJ is John and Jan Portman Professor.

JD is a National Science Foundation pre-doctoral fellow.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • Cell Biology
  • Epigenetic DNA methylation
  • DNMT
  • Gene expression
  • Flow
  • Shear stress
  • Endothelial function
  • Atherosclerosis

The role of epigenetics in the endothelial cell shear stress response and atherosclerosis


Journal Title:

International Journal of Biochemistry and Cell Biology


Volume 67


, Pages 167-176

Type of Work:

Article | Post-print: After Peer Review


Currently in the field of vascular biology, the role of epigenetics in endothelial cell biology and vascular disease has attracted more in-depth study. Using both in vitro and in vivo models of blood flow, investigators have recently begun to reveal the underlying epigenetic regulation of endothelial gene expression. Recently, our group, along with two other independent groups, have demonstrated that blood flow controls endothelial gene expression by DNA methyltransferases (DNMT1 and 3A). Disturbed flow (d-flow), characterized by low and oscillating shear stress (OS), is pro-atherogenic and induces expression of DNMT1 both in vivo and in vitro. D-flow regulates genome-wide DNA methylation patterns in a DNMT-dependent manner. The DNMT inhibitor 5-Aza-2’deoxycytidine (5Aza) or DNMT1 siRNA reduces OS-induced endothelial inflammation. Moreover, 5Aza inhibits the development of atherosclerosis in ApoE-/- mice. Through a systems biological analysis of genome-wide DNA methylation patterns and gene expression data, we found 11 mechanosensitive genes which were suppressed by d-flow in vivo, experienced hypermethylation in their promoter region in response to d-flow, and were rescued by 5Aza treatment. Interestingly, among these mechanosensitive genes, the two transcription factors HoxA5 and Klf3 contain cAMP-response-elements (CRE), which may indicate that methylation of CRE sites could serve as a mechanosensitive master switch in gene expression. These findings provide new insight into the mechanism by which flow controls epigenetic DNA methylation patterns, which in turn alters endothelial gene expression, regulates vascular biology, and induces atherosclerosis. These novel findings have broad implications for understanding the biochemical mechanisms of atherogenesis and provide a basis for identifying potential therapeutic targets for atherosclerosis.

Copyright information:

© 2015 Elsevier Ltd.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Creative Commons License

Export to EndNote