Abstract
Chronic low-grade vascular inflammation and endothelial dysfunction significantly contribute to the pathogenesis of cardiovascular diseases. In endothelial cells (ECs), anti-inflammatory or pro-inflammatory signaling can be induced by different patterns of the fluid shear stress (SS) exerted by blood flow on ECs. Laminar blood flow with high magnitude is anti-inflammatory, while disturbed flow and laminar flow with low magnitude is pro-inflammatory. Endothelial mechanosensors are the key upstream signaling proteins in SS-induced pro- and anti-inflammatory responses. Being transmembrane proteins, mechanosensors, not only experience fluid SS but also become regulated by the biomechanical properties of the lipid bilayer and the cytoskeleton. We review the apparent effects of pro-inflammatory factors (hypoxia, oxidative stress, hypercholesterolemia, and cytokines) on the biomechanics of the lipid bilayer and the cytoskeleton. An analysis of the available data suggests that the formation of a vicious circle may occur, in which pro-inflammatory cytokines enhance and attenuate SS-induced pro-inflammatory and anti-inflammatory signaling, respectively.
Highlights
We proposed that the gradients in hydrostatic pressures across the plasma membrane induced by changes in cell volume are actively probed by cells via the pulling activity of non-muscle myosin II (NMMII) and the pushing activity of submembrane actin-based CSK (smACSK) [64]
Considering the forces arising from the lipid bilayer, and the forces generated by smACSK, the energy input (E(intracellular)) that is received—in addition to extracellular mechanical forces—by any single mechanosensory can be presented as the sum of the following energies: E(intracellular) = E(lipid bilayer) + E(NMMII) + E(protrusion) + E(resistance) + E(smACSK spring) where E(lipid bilayer) is an energy from the lipid bilayer, E(NMMII) is an energy of NMMIIgenerated pulling force, E(protrusion) is an energy of pushing force due to the actin-based assembly of lamellipodia and filopodia, E(resistance) is an energy generated by the lipid bilayer together with smACSK, and
The experimental data considered here suggest that internal cellular forces—mainly NMMII contractility and actin-based lamellipodial protrusions, together with pro-inflammatory cholesterol- and oxidative stress-induced changes in the biomechanics of the lipid bilayer—
Summary
Inflammation is a key mechanism affecting endothelial cells (ECs) and leading to atherosclerosis [1,2,3,4]. The molecular pathways leading to inflammation in ECs begin at the endothelial mechanosensors, one of which is the platelet endothelial cell adhesion molecule-1 (PECAM1), which forms a mechanosensory complex with vascular endothelial cadherin (VEcadherin) and vascular endothelial growth factor receptor 2 (VEGFR2). ApoE−/− mice [16,17] These links between blood flow patterns, the mechanosensitivity of ECs, and inflammation evoked deep interest in the study of endothelial mechanosensors [18,19,20,21,22,23,24,25,26,27], which include primary cilia, glycocalyx, integrins, caveolae, ion channels, heterotrimeric G proteins, G protein-coupled receptors (GPCRs), PECAM-1, VE-cadherin, VEGFR2, and the. In human pulmonary aortic ECs (HPAECs), mitochondria respond to fluid SS with increased oxidative phosphorylation and elevated ATP production [30,31], suggesting their possible role as mechanosensors
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
