Shear stress increases endothelial hyaluronan synthase 2 and hyaluronan synthesis especially in regard to an atheroprotective flow profile

Abstract

Recent studies revealed that in vivo the inner blood vessel surface is lined with an endothelial surface layer at least 0.5 μm thick, which serves as an aegis, protecting the vessel wall from arteriosclerosis. Hyaluronan seems to be a constitutive component in regard to the atheroprotective properties of this surface structure. It has been shown that arterial pulsatile laminar blood flow increases the thickness of this surface layer in vivo, while it is significantly reduced at atheroprone regions with disturbed flow. This study was undertaken to reveal whether endothelial hyaluronan synthesis via hyaluronan synthase 2 (HAS2) can be changed by different shear stress conditions in vitro, especially in regard to an undisturbed, arteriallike pulsatile flow profile. Human umbilical vein endothelial cells, exposed to constant or pulsatile shear stress in a cone-and-plate system, were analysed for HAS2 expression by realtime RT-PCR and immunoblotting, and for hyaluronan by ELISA. Hyaluronan synthase 2 mRNA and protein were found to be transiently increased in a shear stress-dependent manner via the phosphatidylinositol 3-kinase-Akt pathway. Especially pulsatile, arterial-like shear stress conditions induced enzyme and hyaluronan effectively, while lower shear stress that continuously changed its direction did not induce any differences in comparison with control cultures not exposed to shear stress. These experiments provide a link between the production of a constitutive component of the endothelial surface layer by endothelial cells and blood flow.

Hemodynamic shear stress characteristic of atherosclerosis-resistant regions promotes glycocalyx formation in cultured endothelial cells

“…Several earlier studies indicate that shear stress may play an important role in regulating EGL expression: in endothelial cells subjected to flow, GAG synthesis was increased, hyaluronic acid incorporation into EGL was induced, and hyaluronan synthase 2 expression was upregulated (2,19,30). Our study has further shown that exposure to the atheroprotective shear stress waveform for 7 days is necessary for the high and uniform apical cell surface expression of some components of the glycocalyx, such as heparan sulfate and hyaluronic acid, in cultured endothelial cells.…”

Nutrigenomics, the Microbiome, and Gene-Environment Interactions: New Directions in Cardiovascular Disease Research, Prevention, and Treatment

“…Several studies have found evidence of epigenetic changes that alter cardiometabolic disease risk, [139][140][141] including defects in endothelial cell function, abnormal blood flow, inflammation, and plaque formation. [142][143][144][145][146][147] Identification and characterization of common epigenetic outcomes linked to disease manifestations and their interaction with nutrient status may allow the development of specific treatment and intervention measures. [148][149][150][151] Interestingly, the effect of limited or oversaturated nutrient bioavailability on epigenetic states is complex and not necessarily direct.…”

Pulsatile Atheroprone Shear Stress Affects the Expression of Transient Receptor Potential Channels in Human Endothelial Cells

“…These different profiles are represented by an atheroprone prototypic arterial waveform versus an atheroprotective prototypic arterial waveform, which can be replicated in vitro. 4,5 An early reaction of endothelial cells toward shear stress is the activation of flow-sensitive ion channels, proposed to act as flow sensors. 6 Moreover, several subtypes of transient receptor potential (TRP) channels, including transient receptor potential cation channel, subfamily C, member 3 (TRPC3) TRPC6, TRPM7, and TRPV1, have been linked to cardiovascular disease, hypertension, and atherosclerosis.…”