ArticleProceedings of the National Academy of Sciences of the United States of America2014
Syndecan 4 is required for endothelial alignment in flow and atheroprotective signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers.
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The trial behind it
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Who cites it
110 citing papers in PubMed.
- Lower levels of plasma syndecan-4 are associated with loss of body weight and fat-free mass after bariatric surgery.BMC research notes · 2024Trial
- Smooth Muscle Cell Plasticity as a Central Determinant of Plaque Stability.Current atherosclerosis reports · 2026Review
- Plasma Regulates Homeostatic Pulmonary Endothelial Signaling to Mitigate Vascular Leak Following Polytrauma and Hemorrhagic Shock.Shock (Augusta, Ga.) · 2026Article
- Early syndecan-4 upregulation predicts cognitive and pathological trajectories in Alzheimer disease.Alzheimer's research & therapy · 2026Article
- Micropatterning transcriptionally and phenotypically reprograms endothelial cells.Acta biomaterialia · 2026Article
- Mechanoreceptor-mediated adaptations to physical exercise: from acute responses to long-term training effects.Cellular and molecular life sciences : CMLS · 2026Review
- Reduced vascular leakage correlates with breast carcinoma T regulatory cell infiltration but not with metastatic propensity.Molecular oncology · 2026Article
- Article
- Endothelial Surface Glycocalyx in Vascular Functions and Diseases.Advances in experimental medicine and biology · 2026Review
- The Molecular Structure of the Endothelial Glycocalyx. Models to Interpret High-Resolution Imaging of an Ordered Structure for the Molecular Filter at the Microvascular Wall.Advances in experimental medicine and biology · 2026Article
- Endothelial Glycocalyx Turnover in Vascular Health and Disease: Rethinking Endothelial Dysfunction.Annual review of biochemistry · 2025Review
- Reversal of cerebrovascular anomalies in a zebrafish model of vein of Galen aneurysm.Nature cardiovascular research · 2025Article
- 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
- Lymphatic System Development and Function.Current cardiology reports · 2024Review
- Integrating molecular and cellular components of endothelial shear stress mechanotransduction.American journal of physiology. Heart and circulatory physiology · 2024Review
- Extracellular Matrix Components and Mechanosensing Pathways in Health and Disease.Biomolecules · 2024Review
- A comprehensive physics-based model for the brachial Artery's full flow mediated dilation (FMD) response observed during the FMD test.Computers in biology and medicine · 2024Article
- Syndecan 4 is a marker of endothelial inflammation in pathological aging and predicts long-term cardiovascular outcomes in type 2 diabetes.Diabetology & metabolic syndrome · 2024Article
- Latrophilin-2 mediates fluid shear stress mechanotransduction at endothelial junctions.The EMBO journal · 2024Article
- Syndecans in hematopoietic cells and their niches.American journal of physiology. Cell physiology · 2024Review
50 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Atherosclerotic plaque localization correlates with regions of disturbed flow in which endothelial cells (ECs) align poorly, whereas sustained laminar flow correlates with cell alignment in the direction of flow and resistance to atherosclerosis. We now report that in hypercholesterolemic mice, deletion of syndecan 4 (S4(-/-)) drastically increased atherosclerotic plaque burden with the appearance of plaque in normally resistant locations. Strikingly, ECs from the thoracic aortas of S4(-/-) mice were poorly aligned in the direction of the flow. Depletion of S4 in human umbilical vein endothelial cells (HUVECs) using shRNA also inhibited flow-induced alignment in vitro, which was rescued by re-expression of S4. This effect was highly specific, as flow activation of VEGF receptor 2 and NF-κB was normal. S4-depleted ECs aligned in cyclic stretch and even elongated under flow, although nondirectionally. EC alignment was previously found to have a causal role in modulating activation of inflammatory versus antiinflammatory pathways by flow. Consistent with these results, S4-depleted HUVECs in long-term laminar flow showed increased activation of proinflammatory NF-κB and decreased induction of antiinflammatory kruppel-like factor (KLF) 2 and KLF4. Thus, S4 plays a critical role in sensing flow direction to promote cell alignment and inhibit atherosclerosis.
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Registered trials
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