Mechanical regulation of epigenetics in vascular biology and pathobiology

Abstract

Vascular endothelial cells (ECs) and smooth muscle cells (VSMCs) are constantly exposed to haemodynamic forces, including blood flow-induced fluid shear stress and cyclic stretch from blood pressure. These forces modulate vascular cell gene expression and function and, therefore, influence vascular physiology and pathophysiology in health and disease. Epigenetics, including DNA methylation, histone modification/chromatin remodelling and RNA-based machinery, refers to the study of heritable changes in gene expression that occur without changes in the DNA sequence. The role of haemodynamic force-induced epigenetic modifications in the regulation of vascular gene expression and function has recently been elucidated. This review provides an introduction to the epigenetic concepts that relate to vascular physiology and pathophysiology. Through the studies of gene expression, cell proliferation, angiogenesis, migration and pathophysiological states, we present a conceptual framework for understanding how mechanical force-induced epigenetic modifications work to control vascular gene expression and function and, hence, the development of vascular disorders. This research contributes to our knowledge of how the mechanical environment impacts the chromatin state of ECs and VSMCs and the consequent cellular behaviours.

MicroRNA-10a is crucial for endothelial response to different flow patterns via interaction of retinoid acid receptors and histone deacetylases

“…HDAC is another important epigenetic factor that can modulate gene expression and cellular function by removing acetyl groups from critical signaling molecules to suppress their functions (2). Our previous study demonstrated that OS induces the expression of both class I (HDAC-1/2/3) and class II (HDAC-5/7) HDACs and their nuclear accumulation in ECs in vivo and in vitro (6); however, whether HDACs can modulate the EC expression of miRs to modulate vascular biology and pathobiology has not been reported.…”

“…Epigenetics is the study of any potentially stable and ideally heritable changes in gene expression or cellular phenotype without alterations in DNA sequences (2). Epigenetic modulations, including histone modification and RNA-based mechanisms, have been identified to regulate vascular functions (2)(3)(4).…”

“…Epigenetic modulations, including histone modification and RNA-based mechanisms, have been identified to regulate vascular functions (2)(3)(4). Histone deacetylases (HDACs) and microRNAs (miRs) have emerged as two important epigenetic mediators in vascular pathophysiology (2)(3)(4)(5)(6). In previous work, we demonstrated that exposure of ECs to OS induces associations of HDAC-3/5/7 with myocyte enhancer factor-2 (MEF-2) to down-regulate the antiinflammatory gene Krüppel-like factor-2 (KLF-2).…”

Biomechanical regulation of vascular smooth muscle cell functions: from in vitro to in vivo understanding

“…It includes DNA methylation, histone modification/chromatin remodelling and RNA-based machinery. Previous research proved that the mechanical environment regulates cellular functions by modifying the chromatin state of ECs and VSMCs [155]. Recent study provides direct evidence that shear stress regulates VSMC turnover by EC-secreted microRNA-126 in the EC-VSMC co-culture model [156].…”

Featured Article: Temporal responses of human endothelial and smooth muscle cells exposed to uniaxial cyclic tensile strain

“…1,2 In the vascular system, hemodynamic stresses such as tension and shear are required to maintain the structural organization and functional activity of vascular endothelial cells (ECs) and vascular smooth muscle cells (SMCs) which form the vessel wall. [3][4][5] Simply spoken, a shear stress is generated by the pulsatile blood flow and the circumferential stress is caused by the pulsatile blood pressure. 4,6,7 When exposed to mechanical loading, ECs act like mechanical sensors.…”