Cellular and Molecular Bioengineering

, Volume 4, Issue 4, pp 560–578 | Cite as

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

Article

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.

Keywords

Endothelial cell Epigenetics Histone deacetylase MicroRNA Shear stress 

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

Notes

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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Copyright information

© Biomedical Engineering Society 2011

Authors and Affiliations

  1. 1.Department of Bioengineering, Institute of Engineering in MedicineUniversity of California, San DiegoLa JollaUSA
  2. 2.Division of Medical Engineering ResearchNational Health Research InstituteMiaoliTaiwan

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