The role of endothelial glycocalyx components in mechanotransduction of fluid shear stress

Pahakis, Manolis; Kosky, Jason R.; Dull, Randal O.; Tarbell, John M.

doi:10.1016/j.bbrc.2007.01.137

Cited by 343 publications

(371 citation statements)

References 28 publications

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“…2006c) and perhaps eNOS phosphorylation by a glycocalyx‐linked deformation of caveolae (Pahakis et al . 2007). Importantly, the present study demonstrates that a decreased shear stress after the cessation of vasodilator therapy leads to a decrease in eNOS expression, a key mediator of shear stress‐induced angiogenesis: vessel growth is absent in eNOS‐knockout mice (Williams et al .…”

Section: Discussionmentioning

confidence: 99%

Shear stress‐induced angiogenesis in mouse muscle is independent of the vasodilator mechanism and quickly reversible

et al. 2016

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AimIs modulation of skeletal muscle capillary supply by altering blood flow due to a presumptive shear stress response per se, or dependent on the vasodilator mechanism?MethodsThe response to four different vasodilators, and cotreatment with blockers of NO and prostaglandin synthesis, was compared. Femoral artery blood flow was correlated with capillary‐to‐fibre ratio (C:F) and protein levels of putative angiogenic compounds.ResultsAll vasodilators induced a similar increase in blood flow after 14 days, with a similar effect on C:F (1.62 ± 0.05, 1.60 ± 0.01, 1.57 ± 0.06, 1.57 ± 0.07, respectively, all P < 0.05 vs. control 1.20 ± 0.01). Concomitant inhibitors revealed differential effects on blood flow and angiogenesis, demonstrating that a similar response may have different signalling origins. The time course of this response with the most commonly used vasodilator, prazosin, showed that blood flow increased from 0.40 mL min−1 to 0.61 mL min−1 by 28 days (P < 0.05), dropped within 1 week after the cessation of treatment (0.54 mL min−1; P < 0.05) and returned to control levels by 6 weeks. In parallel with FBF, capillary rarefaction began within 1 week (P < 0.05), giving C:F values similar to control by 2 weeks. Of the dominant signalling pathways, prazosin decreased muscle VEGF, but increased its cognate receptor Flk‐1 (both P < 0.01); levels of eNOS varied with blood flow (P < 0.05), and Ang‐1 initially increased, while its receptor Tie‐2 was unchanged, with only modest changes in the antiangiogenic factor TSP‐1.ConclusionHyperaemia‐induced angiogenesis, likely in response to elevated shear stress, is independent of the vasodilator involved, with a rapid induction and quick regression following the stimulus withdrawal.

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Section: Discussionmentioning

confidence: 99%

Shear stress‐induced angiogenesis in mouse muscle is independent of the vasodilator mechanism and quickly reversible

et al. 2016

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“…Flow sensing properties likely reside in the luminal endothelial surface; constituted by the cell membrane and glycocalyx which is acted by flow [6][7][8][9][10][11][12][13]. We have shown that flowinduced responses require endothelial surface layer oligosaccharides and oligosaccharide-recognizing proteins, lectins because a) specific enzymatic hydrolysis of endogenous oligosaccharides or their binding to exogenous lectins exactly alter flow-induced responses and b) infusion of diverse exogenous oligosaccharides that bind to endothelial surface lectins alter the effects of flow [8,11,12].…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, the roles of individual endothelial surface sugars and lectins in flow-induced responses are function biased; a complexity that makes difficult to identify the exact "mechanosensor(s)" for each response [6,8,[10][11][12][13]15]. In contrast, in the case of a defined G-protein coupled receptor, the response triggered by its specific agonist identifies it as the structure of origin, the agonist-sensor [1,3,4,14].…”

Section: Introductionmentioning

confidence: 99%

Flow enhances the agonist-induced responses of the bradykinin receptor (B2) because of its lectinic nature: Role of its oligosaccharide environment

Jiménez-Corona¹,

Espinosa‐Tanguma²,

Knabb³

et al. 2017

J Transl Sci

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Studies in perfused hearts show that flow-sensitive G-protein coupled receptors are lectinic suggesting that flow exerts its effects by modulating the interaction between endothelial surface layer oligosaccharides and lectinic transmembrane G-protein coupled receptors. To test this hypothesis guinea pig carotid arteries were perfused with Krebs-Henseleit at 11 or 16 ml/min. The effects of flow on the contraction induced by stimulating the bradykinin receptor were determined using the flow-induced changes of bradykinin concentration-vascular response curves. Flow effects on the bradykinin receptor were studied in four independent groups; in Groups 1 and 2 (controls) the endothelial surface layer glyosidic composition was not altered, in Group 3 an oligosaccharide polymer that lectinically and irreversibly binds to endothelial surface layer was infused, and in Group 4 endothelial surface layer heparinic were hydrolyzed. Results show that an increase in flow from 11 to 16 ml/min shifted the vascular response curve of bradykinin upward and to the left. Similar results were obtained with endothelial surface layer oligosaccharide polymer binding and heparinic removal but elevation of flow from 11 to 16 ml/min had no effect. Thus, the flow dependence of the lectinic bradykinin receptor depends on its ability to interact with the oligosaccharide environment and heparinic groups.

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“…The glycocalyx layer has been described as a mechanosensor and transducer of FSS on ECs [1,5,[25][26][27][28][29][30][31][32][33][34][35][36]. Theoretical models to describe the transmission of force from fluid flow to the surface of cells covered by glycocalyx have revealed & 2014 The Author(s) Published by the Royal Society.…”

Section: Introductionmentioning

confidence: 99%

Shear-induced force transmission in a multicomponent, multicell model of the endothelium

Dabagh

Jalali

Butler

et al. 2014

J. R. Soc. Interface.

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Haemodynamic forces applied at the apical surface of vascular endothelial cells (ECs) provide the mechanical signals at intracellular organelles and through the inter-connected cellular network. The objective of this study is to quantify the intracellular and intercellular stresses in a confluent vascular EC monolayer. A novel three-dimensional, multiscale and multicomponent model of focally adhered ECs is developed to account for the role of potential mechanosensors (glycocalyx layer, actin cortical layer, nucleus, cytoskeleton, focal adhesions (FAs) and adherens junctions (ADJs)) in mechanotransmission and EC deformation. The overriding issue addressed is the stress amplification in these regions, which may play a role in subcellular localization of mechanotransmission. The model predicts that the stresses are amplified 250-600-fold over apical values at ADJs and 175-200-fold at FAs for ECs exposed to a mean shear stress of 10 dyne cm 22 . Estimates of forces per molecule in the cell attachment points to the external cellular matrix and cell-cell adhesion points are of the order of 8 pN at FAs and as high as 3 pN at ADJs, suggesting that direct force-induced mechanotransmission by single molecules is possible in both. The maximum deformation of an EC in the monolayer is calculated as 400 nm in response to a mean shear stress of 1 Pa applied over the EC surface which is in accord with measurements. The model also predicts that the magnitude of the cell-cell junction inclination angle is independent of the cytoskeleton and glycocalyx. The inclination angle of the cell-cell junction is calculated to be 6.68 in an EC monolayer, which is somewhat below the measured value (9.98) reported previously for ECs subjected to 1.6 Pa shear stress for 30 min. The present model is able, for the first time, to cross the boundaries between different length scales in order to provide a global view of potential locations of mechanotransmission.

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The role of endothelial glycocalyx components in mechanotransduction of fluid shear stress

Cited by 343 publications

References 28 publications

Shear stress‐induced angiogenesis in mouse muscle is independent of the vasodilator mechanism and quickly reversible

Shear stress‐induced angiogenesis in mouse muscle is independent of the vasodilator mechanism and quickly reversible

Flow enhances the agonist-induced responses of the bradykinin receptor (B2) because of its lectinic nature: Role of its oligosaccharide environment

Shear-induced force transmission in a multicomponent, multicell model of the endothelium

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