ArticleProceedings of the National Academy of Sciences of the United States of America2014
Fluid shear stress threshold regulates angiogenic sprouting.
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 196 papers, 1 of them a synthesis that pooled it.
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Who cites it
196 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Recent advancements and future requirements in vascularization of cortical organoids.Frontiers in bioengineering and biotechnology · 2022Pooled it
- Ultrasound Cavitation of Microbubbles Augments Limb Perfusion and Promotes Ulcer Healing in Chronic Limb-Threatening Ischemia.JACC. Cardiovascular imaging · 2026Trial
- Matrix metalloproteinase-mediated degradation governs angioarchitecture within poly(ethylene Glycol) hydrogels.Acta biomaterialia · 2026Article
- Endothelial Hydrogels Improve Microvascular Regeneration and Perfusion in Tracheal Scaffolds.The Laryngoscope · 2026Article
- Computational fluid dynamics enables predictable scale-up of perfusion bioreactors for microvessel production.PNAS nexus · 2026Article
- 4D force patterning enables spatial control of angiogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Hemodynamic Metrics and Arterial Dysfunction: Insights From a Novel Microfluidic Device.International journal for numerical methods in biomedical engineering · 2026Article
- Computational Modeling Unveils the Impact of Tissue Growth and Vascular Remodeling on the Distribution of Interstitial Chemical Species.Annals of biomedical engineering · 2026Article
- Kidney organoid vascularization: current advancements in the field.Regenerative therapy · 2026Article
- Advances in In Vitro Vascularization of Engineered Tissues: From Microvessel Formation to Hepatic Tissue Integration.Regenerative therapy · 2026Article
- ETV2 Mediated Differentiation of Human Pluripotent Stem Cells Results in Functional Endothelial Cells for Engineering Advanced Vascularized Microphysiological Models.Advanced healthcare materials · 2026Article
- Mechanoreceptor-mediated adaptations to physical exercise: from acute responses to long-term training effects.Cellular and molecular life sciences : CMLS · 2026Review
- Fluid shear stress activates a targetable mechano-metastatic cascade to promote medulloblastoma metastasis.Nature biomedical engineering · 2026Article
- Multi-scale Engineered Vasculature and Hierarchical Porosity via Volumetric Bioprinting-Guided Photopolymerization-Induced Phase Separation.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- The Effect of Mechanical Loading on Sprouting Angiogenesis from Engineered Macro-vessel Model.Small methods · 2026Article
- Increasing complexity in vascular microphysiological systems: considerations and advances for disease modeling.Frontiers in bioengineering and biotechnology · 2026Review
- Predicting red blood cell transport and capillary hemodynamics in angiogenic and tumor vascular networks in silico.Biophysical journal · 2025Article
- Microengineered patient-derived endometrium-on-a-chip for the evaluation of endometrial receptivity and personalised translational medicine.Nature communications · 2025Article
- Organ-on-a-Chip Models of the Female Reproductive System: Current Progress and Future Perspectives.Micromachines · 2025Review
- Temporal dynamics of angiogenesis: the emerging role of mechanoregulated pathways.Biochemical Society transactions · 2025Review
136 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors.
Funding
Abstract
The density and architecture of capillary beds that form within a tissue depend on many factors, including local metabolic demand and blood flow. Here, using microfluidic control of local fluid mechanics, we show the existence of a previously unappreciated flow-induced shear stress threshold that triggers angiogenic sprouting. Both intraluminal shear stress over the endothelium and transmural flow through the endothelium above 10 dyn/cm(2) triggered endothelial cells to sprout and invade into the underlying matrix, and this threshold is not impacted by the maturation of cell-cell junctions or pressure gradient across the monolayer. Antagonizing VE-cadherin widened cell-cell junctions and reduced the applied shear stress for a given transmural flow rate, but did not affect the shear threshold for sprouting. Furthermore, both transmural and luminal flow induced expression of matrix metalloproteinase 1, and this up-regulation was required for the flow-induced sprouting. Once sprouting was initiated, continuous flow was needed to both sustain sprouting and prevent retraction. To explore the potential ramifications of a shear threshold on the spatial patterning of new sprouts, we used finite-element modeling to predict fluid shear in a variety of geometric settings and then experimentally demonstrated that transmural flow guided preferential sprouting toward paths of draining interstitial fluid flow as might occur to connect capillary beds to venules or lymphatics. In addition, we show that luminal shear increases in local narrowings of vessels to trigger sprouting, perhaps ultimately to normalize shear stress across the vasculature. Together, these studies highlight the role of shear stress in controlling angiogenic sprouting and offer a potential homeostatic mechanism for regulating vascular density.
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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.