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



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.


Endothelial cell Epigenetics Histone deacetylase MicroRNA Shear stress 



3′-untranslated region.


activator protein-1


apolipoprotein E-deficient


cellular caspase-8 (FLICE)-like inhibitory protein


DNA methyltransferase


endothelial cell


endothelial nitric oxide synthase


estrogen receptor


extracellular-regulated kinase


fibroblast growth factor


forkhead box protein O1


histone acetyltransferase


histone deacetylase


histone N-methyltransferase


human umbilical vein endothelial cell


intercellular adhesion molecule-1




krüppel-like factor 2


low density lipoprotein


laminar shear stress


mitogen-activated protein kinase


methyl-CpG-binding domain


monocyte chemotactic protein-1


methyl CpG binding protein 2


myocyte enhancer factor-2




noncoding RNA


nuclear factor-κB


nitric oxide


oscillatory shear stress


oxide low density lipoprotein




peroxisome proliferators-activated receptor


precursor microRNA


primary microRNA


pulsatile shear stress


sirtuin, information regulator


information regulator 2


smooth muscle cell


signal transducer and activator of transcription 5A


tumor necrosis factor-α


trichostatin A


vascular adhesion molecule-1


vascular endothelial growth factor



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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