Shear-induced endothelial mechanotransduction: The interplay between reactive oxygen species (ROS) and nitric oxide (NO) and the pathophysiological implications
Journal
Journal of Biomedical Science
Journal Volume
21
Journal Issue
1
Pages
-
Date Issued
2014
Author(s)
Abstract
Hemodynamic shear stress, the blood flow-generated frictional force acting on the vascular endothelial cells, is essential for endothelial homeostasis under normal physiological conditions. Mechanosensors on endothelial cells detect shear stress and transduce it into biochemical signals to trigger vascular adaptive responses. Among the various shear-induced signaling molecules, reactive oxygen species (ROS) and nitric oxide (NO) have been implicated in vascular homeostasis and diseases. In this review, we explore the molecular, cellular, and vascular processes arising from shear-induced signaling (mechanotransduction) with emphasis on the roles of ROS and NO, and also discuss the mechanisms that may lead to excessive vascular remodeling and thus drive pathobiologic processes responsible for atherosclerosis. Current evidence suggests that NADPH oxidase is one of main cellular sources of ROS generation in endothelial cells under flow condition. Flow patterns and magnitude of shear determine the amount of ROS produced by endothelial cells, usually an irregular flow pattern (disturbed or oscillatory) producing higher levels of ROS than a regular flow pattern (steady or pulsatile). ROS production is closely linked to NO generation and elevated levels of ROS lead to low NO bioavailability, as is often observed in endothelial cells exposed to irregular flow. The low NO bioavailability is partly caused by the reaction of ROS with NO to form peroxynitrite, a key molecule which may initiate many pro-atherogenic events. This differential production of ROS and RNS (reactive nitrogen species) under various flow patterns and conditions modulates endothelial gene expression and thus results in differential vascular responses. Moreover, ROS/RNS are able to promote specific post-translational modifications in regulatory proteins (including S-glutathionylation, S-nitrosylation and tyrosine nitration), which constitute chemical signals that are relevant in cardiovascular pathophysiology. Overall, the dynamic interplay between local hemodynamic milieu and the resulting oxidative and S-nitrosative modification of regulatory proteins is important for ensuing vascular homeostasis. Based on available evidence, it is proposed that a regular flow pattern produces lower levels of ROS and higher NO bioavailability, creating an anti-atherogenic environment. On the other hand, an irregular flow pattern results in higher levels of ROS and yet lower NO bioavailability, thus triggering pro-atherogenic effects. ? 2014 Hsieh et al.; licensee BioMed Central Ltd.
Subjects
Endothelial cell; Flow pattern; Mechanotransduction; Nitric oxide (NO); Reactive oxygen species (ROS); Shear stress
SDGs
Other Subjects
calcium calmodulin dependent protein kinase II; calmodulin; endothelial leukocyte adhesion molecule 1; endothelial nitric oxide synthase; heme oxygenase 1; hydroxymethylglutaryl coenzyme A reductase kinase; immunoglobulin enhancer binding protein; intercellular adhesion molecule 1; kruppel like factor 2; messenger RNA; monocyte chemotactic protein 1; nitric oxide; oxidized low density lipoprotein; peroxynitrite; reactive nitrogen species; reactive oxygen metabolite; reduced nicotinamide adenine dinucleotide phosphate oxidase; regulator protein; superoxide; thioredoxin 1; thioredoxin reductase 1; transcription factor AP 1; transcription factor Nrf2; tyrosine; unclassified drug; uncoupled endothelial nitric oxide synthase; vascular cell adhesion molecule 1; xanthine oxidase; nitric oxide; reactive oxygen metabolite; antioxidant responsive element; atherogenesis; blood vessel reactivity; cardiovascular disease; disease association; endothelial dysfunction; endothelium cell; enzyme activation; enzyme activity; enzyme phosphorylation; flow kinetics; gene expression regulation; hemodynamics; homeostasis; laminar flow; mechanotransduction; mitochondrial membrane potential; mitochondrial respiration; nitration; nitrosylation; oscillation; oxidation reduction reaction; oxidative phosphorylation; pathophysiology; priority journal; protein binding; protein expression; protein modification; protein processing; proton transport; pulsatile flow; review; s glutathionylation; s nitrosylation; shear stress; tyrosine nitration; vascular endothelium; genetics; hemodynamics; human; mechanical stress; mechanotransduction; metabolism; oxidative stress; signal transduction; Hemodynamics; Humans; Mechanotransduction, Cellular; Nitric Oxide; Oxidative Stress; Protein Processing, Post-Translational; Reactive Nitrogen Species; Reactive Oxygen Species; Signal Transduction; Stress, Mechanical
Type
journal article