Endothelial Cell Mechanotransduction in the Dynamic Vascular Environment

Abstract

The vascular endothelial cells (ECs) that line the inner layer of blood vessels are responsible for maintaining vascular homeostasis under physiological conditions. In the presence of disease or injury, ECs can become dysfunctional and contribute to a progressive decline in vascular health. ECs are constantly exposed to a variety of dynamic mechanical stimuli, including hemodynamic shear stress, pulsatile stretch, and passive signaling cues derived from the extracellular matrix. This review describes the molecular mechanisms by which ECs perceive and interpret these mechanical signals. The translational applications of mechanosensing are then discussed in the context of endothelial-to-mesenchymal transition and engineering of vascular grafts.

Biofabrication Strategies and Engineered In Vitro Systems for Vascular Mechanobiology

“…Traditionally, the influence of fluid shear stress and associated traction forces and strains on endothelial cell (EC) physiology and function have been studied in reductionist models (e.g., parallel plate flow chambers, 2D substrates, transwell inserts). [ 7,8,37,38 ] These studies have provided significant insights into critical aspects of vascular morphogenesis, differentiation, barrier function, diffusional transport, and paracrine signaling mechanisms. In particular, these models are excellent for decoupling the roles of several interconnected flow parameters with complex associations on vascular processes.…”

“…VEGF, PDGF, and surface receptor expression, e.g., Ang‐1, ‐2), and 4) inflammation (via induced expression of E‐selectin, intercellular adhesion molecule (ICAM)‐1, or vascular cell adhesion molecule (VCAM)‐1 in response to inflammatory molecules, (interleukin (IL)‐1β, tumor necrosis factor (TNF)‐α, interferon (IFN)‐γ, or reactive oxygen species (ROS)). [ 7,8 ]…”

“…The endothelial glycocalyx, a brush‐like, nm‐thick layer composed of proteoglycans, glycoproteins, and glycosaminoglycans (GAGs), is present on the luminal EC surface and acts a mechanosensory intermediate between blood flow and the plasma membrane. [ 7,8,94 ] The EC luminal surface also hosts reversibly gated ion channels (pores formed by transmembrane proteins), which permit coordinated exchange of Na + , Ca 2+ , K + , and Cl − ions in response to hemodynamic variations and stretch‐ and strain‐induced perturbations. Mechanical sensing of hemodynamic perturbations is also mediated by the EC plasma membrane via conformational changes in transmembrane proteins and the lipid bilayer, variations in local membrane fluidity and stiffness, engagement of lipid rafts and caveoli, and stimulation of G‐protein‐coupled receptors (GPCRs).…”

“…[ 4 ] Past research has implicated several factors, which regulate vascular structure and function at the cellular and tissue level, including hemodynamic variations, traction forces at the endothelial substratum, extracellular matrix (ECM) characteristics, cell–cell, and cell–matrix interactions, and others. [ 5–11 ] Comprehensive mechanistic investigation of these processes is necessary to understand disease progression and ultimately develop therapeutic strategies to prevent and mitigate chronic and acute vascular pathologies.…”

Interaktion zwischen Muskel und Knochen – ein Wechselspiel zwischen Physik und Biologie

“…Geweberegeneration ist sowohl im Knochen als auch in der Muskulatur stark mit der Angiogenese verknüpft. Endothelzellen werden hauptsächlich über YAP/TAZ-Signalkaskaden und über NOTCHvermittelte Signale reguliert, und beide Kaskaden reagieren stark auf mechanische Reize [52,67]. Es ist daher anzunehmen, dass in die Zirkulation abgegebene angiogene Faktoren wechselweise auf beide Gewebe Einfluss nehmen.…”