ArticleIntegrative biology : quantitative biosciences from nano to macro2014
Shear-induced endothelial NOS activation and remodeling via heparan sulfate, glypican-1, and syndecan-1.
Article in Integrative biology : quantitative biosciences from nano to macro, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
123 citing papers in PubMed, 209 citations in OpenAlex.
- Trial
- L-Arginine and B vitamins improve endothelial function in subjects with mild to moderate blood pressure elevation.European journal of nutrition · 2018Trial
- KNG-1, HSPG and Robo4 reflect hypertension-driven subclinical renal alterations and provide incremental diagnostic value in type 2 diabetic nephropathy.Scientific reports · 2026Article
- PET-microplastics trigger endothelial glycocalyx loss via ER stress and ROS unleashing IL-1β-driven SMC switching and early aortic structural impairment.Journal of nanobiotechnology · 2026Article
- ADAM17-induced shedding of glypican-1 as a mechanism of impaired endothelial shear stress mechanotransduction.American journal of physiology. Cell physiology · 2026Article
- Flow transports extracellular lipid-anchored proteins across the surface of living COS-7 cells.Biophysical journal · 2026Article
- Multimodal Profiling Reveals Distinct Endothelial Activation Pathways Regulated by Flow and Heparan Sulfate.Cellular and molecular bioengineering · 2026Article
- Article
- Glycocalyx strengthens endothelial barrier function and protects from angioedema inducing compounds.Frontiers in immunology · 2026Article
- Mild traumatic brain injury promotes chronic cerebrovascular inflammation and glymphatic suppression.Molecular neurodegeneration advances · 2026Article
- Flow transports extracellular lipid-anchored proteins across the surface of living COS-7 cells.bioRxiv : the preprint server for biology · 2025Article
- Mechanobiology of the blood-brain barrier during development, disease and ageing.Nature communications · 2025Review
- Article
- Endothelial Glycocalyx Turnover in Vascular Health and Disease: Rethinking Endothelial Dysfunction.Annual review of biochemistry · 2025Review
- Evaluation of circulating glypican 4 as a novel biomarker in disease - A comprehensive review.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Article
- Glycocalyx disruption, endothelial dysfunction and vascular remodeling as underlying mechanisms and treatment targets of chronic venous disease.International angiology : a journal of the International Union of Angiology · 2024Review
- AMP dependent protein kinase regulates endothelial heparan sulfate expression in response to an inflammatory stimulus under arterial shear stress.Biochemical and biophysical research communications · 2024Article
- Chemical mapping of the surface interactome of PIEZO1 identifies CADM1 as a modulator of channel inactivation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Integrating molecular and cellular components of endothelial shear stress mechanotransduction.American journal of physiology. Heart and circulatory physiology · 2024Review
63 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
Mammalian epithelial cells are coated with a multifunctional surface glycocalyx (GCX). On vascular endothelial cells (EC), intact GCX is atheroprotective. It is degraded in many vascular diseases. GCX heparan sulfate (HS) is essential for healthy flow-induced EC nitric oxide (NO) release, elongation, and alignment. The HS core protein mechanisms involved in these processes are unknown. We hypothesized that the glypican-1 (GPC1) HS core protein mediates flow-induced EC NO synthase (eNOS) activation because GPC1 is anchored to caveolae where eNOS resides. We also hypothesized that the HS core protein syndecan-1 (SDC1) mediates flow-induced EC elongation and alignment because SDC1 is linked to the cytoskeleton which impacts cell shape. We tested our hypotheses by exposing EC monolayers treated with HS degrading heparinase III (HepIII), and monolayers with RNA-silenced GPC1, or SDC1, to 3 to 24 hours of physiological shear stress. Shear-conditioned EC with intact GCX exhibited characteristic eNOS activation in short-term flow conditions. After long-term exposure, EC with intact GCX were elongated and aligned in the direction of flow. HS removal and GPC1 inhibition, not SDC1 reduction, blocked shear-induced eNOS activation. EC remodeling in response to flow was attenuated by HS degradation and in the absence of SDC1, but preserved with GPC1 knockdown. These findings clearly demonstrate that HS is involved in both centralized and decentralized GCX-mediated mechanotransduction mechanisms, with GPC1 acting as a centralized mechanotransmission agent and SDC1 functioning in decentralized mechanotransmission. This foundational work demonstrates how EC can transform fluid shear forces into diverse biomolecular and biomechanical responses.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.