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 flowinduced 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.