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Epigenetic Regulation of Vascular Endothelial Biology/Pathobiology and Response to Fluid Shear Stress

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Abstract

Vascular endothelial cells (ECs) are constantly exposed to hemodynamic forces, including blood flow-induced shear stress, which modulates EC gene expression and function and hence vascular biology/pathobiology in health and disease. Epigenetics refers to chromatin-based mechanisms, including DNA methylation, histone modifications, and RNA-based machinery, which regulate gene expression without changes in the underlying DNA sequences. The role of epigenetic mechanisms in regulating EC gene expression and function under static condition and in response to shear stress has recently emerged. This review provides an introduction to epigenetic concepts for vascular bioengineers and biologists. Using endothelial nitric oxide synthase, angiogenesis, and atherogenesis as examples, this review presents a conceptual framework for understanding how epigenetic factors, including histone deacetylases and microRNAs, are involved in the control of EC gene expression and function and hence vascular disease development, and summarizes the current knowledge on the role of epigenetic pathways in regulating EC responses to shear stress. Such information can contribute to our understanding of how mechanical environment of ECs impacts their genome to modify disease susceptibility and help to generate new approaches for therapeutic interventions.

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Abbreviations

3′-UTR:

3′-untranslated region.

AP-1:

activator protein-1

apoE−/− :

apolipoprotein E-deficient

cFLIP:

cellular caspase-8 (FLICE)-like inhibitory protein

DNMT:

DNA methyltransferase

EC:

endothelial cell

eNOS:

endothelial nitric oxide synthase

ER:

estrogen receptor

ERK:

extracellular-regulated kinase

FGF:

fibroblast growth factor

FoxO1:

forkhead box protein O1

HAT:

histone acetyltransferase

HDAC:

histone deacetylase

HMT:

histone N-methyltransferase

HUVEC:

human umbilical vein endothelial cell

ICAM-1:

intercellular adhesion molecule-1

IL:

interleukin

KLF-2:

krüppel-like factor 2

LDL:

low density lipoprotein

LSS:

laminar shear stress

MAPK:

mitogen-activated protein kinase

MBD:

methyl-CpG-binding domain

MCP-1:

monocyte chemotactic protein-1

MeCP2:

methyl CpG binding protein 2

MEF-2:

myocyte enhancer factor-2

miR:

microRNA

ncRNA:

noncoding RNA

NF-κB:

nuclear factor-κB

NO:

nitric oxide

OSS:

oscillatory shear stress

oxLDL:

oxide low density lipoprotein

PI3K:

phosphoinositide-3-kinase

PPAR:

peroxisome proliferators-activated receptor

pre-miR:

precursor microRNA

pri-miR:

primary microRNA

PSS:

pulsatile shear stress

SIRT:

sirtuin, information regulator

Sir2:

information regulator 2

SMC:

smooth muscle cell

STAT5A:

signal transducer and activator of transcription 5A

TNF-α:

tumor necrosis factor-α

TSA:

trichostatin A

VCAM-1:

vascular adhesion molecule-1

VEGF:

vascular endothelial growth factor

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Acknowledgments

This work was supported by National Science Council (Taiwan) Grants 99-2321-B-400-002 and NRPB-CV013 and National Health Research Institutes (Taiwan) Grant ME-099-PP-06. This article is a tribute to professor Shu Chien, a pioneer in the fields of bioengineering, mechanobiology, biorheology, and vascular physiology and a leading expert on how blood flow affects vessels and hence cardiovascular pathologies, for his 80th birthday.

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  1. Department of Bioengineering, Institute of Engineering in Medicine, University of California, San Diego, La Jolla, CA, 92093, USA

    Jing Zhou

  2. Division of Medical Engineering Research, National Health Research Institute, Miaoli, 350, Taiwan

    Seh Hong Lim & Jeng-Jiann Chiu

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  1. Jing Zhou
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Associate Editors John Shyy and Yingxiao Wang oversaw the review of this article.

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Zhou, J., Lim, S.H. & Chiu, JJ. Epigenetic Regulation of Vascular Endothelial Biology/Pathobiology and Response to Fluid Shear Stress. Cel. Mol. Bioeng. 4, 560–578 (2011). https://doi.org/10.1007/s12195-011-0199-2

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