Effect of Continuous Supression of Heparan Sulfate on Arterial Endothelial Alignment and Gene Expression Under Several Shear Stress Waveforms

2010 ◽  
Author(s):  
Charles S. Wallace ◽  
Morton H. Friedman
Keyword(s):  
Gene Expression ◽  
Shear Stress ◽  
Heparan Sulfate ◽  
G Proteins ◽  
Carotid Arteries ◽  
Sialic Acids ◽  
Endothelial Glycocalyx ◽  
Luminal Surface ◽  
Gel Layer ◽  
Junction Proteins

The literature suggests that endothelial cells (ECs) possess many molecules that have mechanosensor capabilities, such as intracellular junction proteins, G proteins, ion channels, integrins, and the glycocalyx [1]. The endothelial glycocalyx is located on the luminal surface of ECs and interacts with the passing blood, thus making it a strong mechanosensor candidate. The glycocalyx is a negatively charged gel layer ranging from 0.5 μm thick in capillaries to 4.5 μm thick in carotid arteries [2]. The glycocalyx consists primarily of sialic acids, chondroitin sulfate, hyaluronic acid, and heparan sulfate (HS). HS is the most abundant glycosaminoglycan within the glycocalyx, and it is one of the most studied molecules in this layer [3].

Maturation enhances fluid shear-induced activation of eNOS in perfused ovine carotid arteries

2005 ◽  
Vol 289 (5) ◽  
pp. H2220-H2227 ◽  
Author(s):  
Charles Ray White ◽  
Mohammad Wael Hamade ◽  
Koushan Siami ◽  
Melody M. Chang ◽  
Anandit Mangalwadi ◽  
...  
Keyword(s):  
Shear Stress ◽  
Surface Area ◽  
Carotid Arteries ◽  
Fluid Shear Stress ◽  
Specific Activity ◽  
Luminal Surface ◽  
Fluid Shear ◽  
No Release ◽  
Age Dependent ◽  
Enos Protein

The present study tests the hypothesis that age-dependent increases in endothelial vasodilator capacity are due to maturational increases in endothelial nitric oxide (NO) synthesis and release. Intact 4-cm carotid artery segments taken from term fetal lambs and nonpregnant adult sheep were perfused by using a closed system that enabled independent control of flow and inflow pressure and facilitated complete recovery of all NO released. Fluid shear stress induced a graded release of NO (in nmol NO·min·cm−2of luminal surface area) that was significantly greater in adult (890 ± 140) than in fetal (300 ± 40) carotid arteries at corresponding values of shear stress (5.9 ± 0.3 dyn/cm2) but was independent of inflow pressure in both age groups. These age-related differences in NO release were not attributable to corresponding differences in endothelial NO synthase (eNOS) abundance, as eNOS protein levels (in ng of eNOS/cm2of luminal surface area) were similar in adult (14 ± 2) and fetal (12 ± 1) arteries. Adult (80 ± 15) and fetal (89 ± 32) levels of eNOS mRNA (in 106copies/cm2of luminal surface area) were also similar. However, when NO release was normalized relative to the associated mass of eNOS protein to estimate eNOS-specific activity in situ, this value (in nmol NO·μg of eNOS−1·min−1) was significantly greater in adult (177 ± 44) than in fetal (97 ± 36) arteries when the endothelium was maximally activated by A-23187. Similarly, the slope of the relation between fluid shear stress and estimated eNOS-specific activity (in nmol NO·μg of eNOS−1·min−1per dyn/cm2) was also significantly greater in adult (6.8 ± 0.1) than in fetal (2.9 ± 0.1) arteries, which suggests that eNOS may be more sensitive to or more efficiently coupled to activating stimuli in adult compared with fetal arteries. We conclude that maturational increases in endothelial vasodilator capacity are attributable to age-dependent increases in NO release secondary to elevated eNOS-specific activity and involve more efficient coupling between endothelial activation and enhancement of eNOS activity in adult compared with fetal arteries.

scholarly journals Fluid shear stress induces the clustering of heparan sulfate via mobility of glypican-1 in lipid rafts

2013 ◽  
Vol 305 (6) ◽  
pp. H811-H820 ◽  
Author(s):  
Ye Zeng ◽  
Michele Waters ◽  
Allison Andrews ◽  
Peyman Honarmandi ◽  
Eno E. Ebong ◽  
...  
Keyword(s):  
Shear Stress ◽  
Heparan Sulfate ◽  
Lipid Rafts ◽  
Fluid Shear Stress ◽  
Cell Junctions ◽  
Endothelial Glycocalyx ◽  
Membrane Rafts ◽  
Cholera Toxin B Subunit ◽  
Fluid Shear ◽  
Caveolin 1

The endothelial glycocalyx plays important roles in mechanotransduction. We recently investigated the distribution and interaction of glycocalyx components on statically cultured endothelial cells. In the present study, we further explored the unknown organization of the glycocalyx during early exposure (first 30 min) to shear stress and tested the hypothesis that proteoglycans with glycosaminoglycans, which are localized in different lipid microdomains, respond distinctly to shear stress. During the initial 30 min of exposure to shear stress, the very early responses of the glycocalyx and membrane rafts were detected using confocal microscopy. We observed that heparan sulfate (HS) and glypican-1 clustered in the cell junctions. In contrast, chondroitin sulfate (CS), bound albumin, and syndecan-1 did not move. The caveolae marker caveolin-1 did not move, indicating that caveolae are anchored sufficiently to resist shear stress during the 30 min of exposure. Shear stress induced significant changes in the distribution of ganglioside GM1 (a marker for membrane rafts labeled with cholera toxin B subunit). These data suggest that fluid shear stress induced the cell junctional clustering of lipid rafts with their anchored glypican-1 and associated HS. In contrast, the mobility of CS, transmembrane bound syndecan-1, and caveolae were constrained during exposure to shear stress. This study illuminates the role of changes in glycocalyx organization that underlie mechanisms of mechanotransduction.

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

2013 ◽  
Vol 304 (2) ◽  
pp. C137-C146 ◽  
Author(s):  
Andrew Koo ◽  
C. Forbes Dewey ◽  
Guillermo García-Cardeña
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Heparan Sulfate ◽  
Vascular Endothelial Cells ◽  
Surface Expression ◽  
Endothelial Glycocalyx ◽  
Cell Surface Expression ◽  
Apical Surface ◽  
Laminar Shear Stress ◽  
Critical Components

The endothelial glycocalyx, a glycosaminoglycan layer located on the apical surface of vascular endothelial cells, has been shown to be important for several endothelial functions. Previous studies have documented that the glycocalyx is highly abundant in the mouse common carotid region, where the endothelium is exposed to laminar shear stress, and it is resistant to atherosclerosis. In contrast, the glycocalyx is scarce or absent in the mouse internal carotid sinus region, an area exposed to nonlaminar shear stress and highly susceptible to atherosclerosis. On the basis of these observations, we hypothesized that the expression of components of the endothelial glycocalyx is differentially regulated by distinct hemodynamic environments. To test this hypothesis, human endothelial cells were exposed to shear stress waveforms characteristic of atherosclerosis-resistant or atherosclerosis-susceptible regions of the human carotid, and the expression of several components of the glycocalyx was assessed. These experiments revealed that expression of several components of the endothelial glycocalyx is differentially regulated by distinct shear stress waveforms. Interestingly, we found that heparan sulfate expression is increased and evenly distributed on the apical surface of endothelial cells exposed to the atheroprotective waveform and is irregularly present in cells exposed to the atheroprone waveform. Furthermore, expression of a heparan sulfate proteoglycan, syndecan-1, is also differentially regulated by the two waveforms, and its suppression mutes the atheroprotective flow-induced cell surface expression of heparan sulfate. Collectively, these data link distinct hemodynamic environments to the differential expression of critical components of the endothelial glycocalyx.

Evidence that gene expression of ovarian follicular tight junction proteins is regulated in vivo and in vitro in cattle

2017 ◽  
Vol 95 (3) ◽  
pp. 1313 ◽  
Author(s):  
L. Zhang ◽  
L. F. Schütz ◽  
C. L. Robinson ◽  
M. L. Totty ◽  
L. J. Spicer
Keyword(s):  
Gene Expression ◽  
Tight Junction ◽  
Tight Junction Proteins ◽  
Junction Proteins

scholarly journals Luminal surface concentration of lipoprotein (LDL) and its effect on the wall uptake of cholesterol by canine carotid arteries

1995 ◽  
Vol 21 (1) ◽  
pp. 135-145 ◽  
Author(s):  
Xiaoyan Deng ◽  
Yves Marois ◽  
Thien How ◽  
Yahye Merhi ◽  
Martin King ◽  
...  
Keyword(s):  
Carotid Arteries ◽  
Surface Concentration ◽  
Luminal Surface

scholarly journals Epigenetic Changes During Mechanically Induced Osteogenic Lineage Commitment

2015 ◽  
Vol 137 (2) ◽  
Author(s):  
Julia C. Chen ◽  
Mardonn Chua ◽  
Raymond B. Bellon ◽  
Christopher R. Jacobs
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Shear Stress ◽  
Fluid Shear Stress ◽  
Methylation Status ◽  
Lineage Commitment ◽  
Fluid Shear ◽  
Osteogenic Lineage ◽  
Osteogenic Markers ◽  
Heterochromatin Structure

Osteogenic lineage commitment is often evaluated by analyzing gene expression. However, many genes are transiently expressed during differentiation. The availability of genes for expression is influenced by epigenetic state, which affects the heterochromatin structure. DNA methylation, a form of epigenetic regulation, is stable and heritable. Therefore, analyzing methylation status may be less temporally dependent and more informative for evaluating lineage commitment. Here we analyzed the effect of mechanical stimulation on osteogenic differentiation by applying fluid shear stress for 24 hr to osteocytes and then applying the osteocyte-conditioned medium (CM) to progenitor cells. We analyzed gene expression and changes in DNA methylation after 24 hr of exposure to the CM using quantitative real-time polymerase chain reaction and bisulfite sequencing. With fluid shear stress stimulation, methylation decreased for both adipogenic and osteogenic markers, which typically increases availability of genes for expression. After only 24 hr of exposure to CM, we also observed increases in expression of later osteogenic markers that are typically observed to increase after seven days or more with biochemical induction. However, we observed a decrease or no change in early osteogenic markers and decreases in adipogenic gene expression. Treatment of a demethylating agent produced an increase in all genes. The results indicate that fluid shear stress stimulation rapidly promotes the availability of genes for expression, but also specifically increases gene expression of later osteogenic markers.

scholarly journals Heart rate reduction with ivabradine promotes shear stress-dependent anti-inflammatory mechanisms in arteries

2016 ◽  
Vol 116 (07) ◽  
pp. 181-190 ◽  
Author(s):  
Luong Le ◽  
Hayley Duckles ◽  
Torsten Schenkel ◽  
Marwa Mahmoud ◽  
Jordi Tremoleda ◽  
...  
Keyword(s):  
Heart Rate ◽  
Shear Stress ◽  
Carotid Arteries ◽  
Vascular Inflammation ◽  
Protective Effects ◽  
En Face ◽  
Inflammatory Activation ◽  
Anti Inflammatory ◽  
Stress Dependent

SummaryBlood flow generates wall shear stress (WSS) which alters endothelial cell (EC) function. Low WSS promotes vascular inflammation and atherosclerosis whereas high uniform WSS is protective. Ivabradine decreases heart rate leading to altered haemodynamics. Besides its cardio-protective effects, ivabradine protects arteries from inflammation and atherosclerosis via unknown mechanisms. We hypothesised that ivabradine protects arteries by increasing WSS to reduce vascular inflammation. Hypercholesterolaemic mice were treated with ivabradine for seven weeks in drinking water or remained untreated as a control. En face immunostaining demonstrated that treatment with ivabradine reduced the expression of pro-inflammatory VCAM-1 (p<0.01) and enhanced the expression of anti-inflammatory eNOS (p<0.01) at the inner curvature of the aorta. We concluded that ivabradine alters EC physiology indirectly via modulation of flow because treatment with ivabradine had no effect in ligated carotid arteries in vivo, and did not influence the basal or TNFα-induced expression of inflammatory (VCAM-1, MCP-1) or protective (eNOS, HMOX1, KLF2, KLF4) genes in cultured EC. We therefore considered whether ivabradine can alter WSS which is a regulator of EC inflammatory activation. Computational fluid dynamics demonstrated that ivabradine treatment reduced heart rate by 20 % and enhanced WSS in the aorta. In conclusion, ivabradine treatment altered haemodynamics in the murine aorta by increasing the magnitude of shear stress. This was accompanied by induction of eNOS and suppression of VCAM-1, whereas ivabradine did not alter EC that could not respond to flow. Thus ivabradine protects arteries by altering local mechanical conditions to trigger an anti-inflammatory response.

scholarly journals Sialic acids regulate microvessel permeability, revealed by novelin vivostudies of endothelial glycocalyx structure and function

2017 ◽  
Vol 595 (15) ◽  
pp. 5015-5035 ◽  
Author(s):  
Kai B. Betteridge ◽  
Kenton P. Arkill ◽  
Christopher R. Neal ◽  
Steven J. Harper ◽  
Rebecca R. Foster ◽  
...  
Keyword(s):  
Sialic Acids ◽  
Structure And Function ◽  
Endothelial Glycocalyx ◽  
Microvessel Permeability ◽  
And Function
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