ArticleBMC biology2022
Atheroprone fluid shear stress-regulated ALK1-Endoglin-SMAD signaling originates from early endosomes.
Article in BMC biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 22 citations in OpenAlex.
- Proteomic Profiling of Endothelial Cells Under Laminar Shear Stress Confirms the Importance of KLF4 in the Regulation of Membrane Protein Expression Compared to Oscillatory Flow.Journal of proteome research · 2026Article
- SIRT6 alleviates ischemic injury via orchestrating the RREB1/Snail and STC1/Smad7 signaling pathways to regulate endothelial-mesenchymal transition.Science China. Life sciences · 2026Article
- The development of intrapulmonary shunting caused by luspatercept in low grade myelodysplastic syndrome: a case report.AME case reports · 2026Article
- A case of hereditary hemorrhagic telangiectasia with hypoxemia onset in the neonatal period.BMC pulmonary medicine · 2025Article
- Engineered Mesenchymal Stem Cell-Derived Extracellular Vesicles Reverse Endothelial-Mesenchymal Transition in Atherosclerosis.Journal of extracellular vesicles · 2025Article
- Identification of Mitophagy-Related Genes and Analysis of Immune Infiltration in Atherosclerosis.Journal of inflammation research · 2025Article
- Extracellular vesicles originating from the mechanical microenvironment in the pathogenesis and applications for cardiovascular diseases.Regenerative therapy · 2024Review
- Endothelial Robo4 suppresses endothelial-to-mesenchymal transition induced by irradiation and improves hematopoietic reconstitution.Cell death & disease · 2024Article
- Shear Stress and Sub-Femtomolar Levels of Ligand Synergize to Activate ALK1 Signaling in Endothelial Cells.Cells · 2024Article
- Capturing physiological hemodynamic flow and mechanosensitive cell signaling in vessel-on-a-chip platforms.Frontiers in physiology · 2024Review
- Biomechanics-mediated endocytosis in atherosclerosis.Frontiers in cardiovascular medicine · 2024Review
- Endothelial cell SMAD6 balances Alk1 function to regulate adherens junctions and hepatic vascular development.Development (Cambridge, England) · 2023Article
- Fluid shear stress-modulated chromatin accessibility reveals the mechano-dependency of endothelial SMAD1/5-mediated gene transcription.iScience · 2023Article
- Review
- Review
- Exosomes: Diagnostic and Therapeutic Implications in Cancer.Pharmaceutics · 2023Review
- Atheroprone fluid shear stress-regulated ALK1-Endoglin-SMAD signaling originates from early endosomes.BMC biology · 2022Article
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFluid shear stress enhances endothelial SMAD1/5 signaling via the BMP9-bound ALK1 receptor complex supported by the co-receptor Endoglin. While moderate SMAD1/5 activation is required to maintain endothelial quiescence, excessive SMAD1/5 signaling promotes endothelial dysfunction. Increased BMP signaling participates in endothelial-to-mesenchymal transition and inflammation culminating in vascular diseases such as atherosclerosis. While the function of Endoglin has so far been described under picomolar concentrations of BMP9 and short-term shear application, we investigated Endoglin under physiological BMP9 and long-term pathophysiological shear conditions.
resultsWe report here that knock-down of Endoglin leads to exacerbated SMAD1/5 phosphorylation and atheroprone gene expression profile in HUVECs sheared for 24 h. Making use of the ligand-trap ALK1-Fc, we furthermore show that this increase is dependent on BMP9/10. Mechanistically, we reveal that long-term exposure of ECs to low laminar shear stress leads to enhanced Endoglin expression and endocytosis of Endoglin in Caveolin-1-positive early endosomes. In these endosomes, we could localize the ALK1-Endoglin complex, labeled BMP9 as well as SMAD1, highlighting Caveolin-1 vesicles as a SMAD signaling compartment in cells exposed to low atheroprone laminar shear stress.
conclusionsWe identified Endoglin to be essential in preventing excessive activation of SMAD1/5 under physiological flow conditions and Caveolin-1-positive early endosomes as a new flow-regulated signaling compartment for BMP9-ALK1-Endoglin signaling axis in atheroprone flow conditions.
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