ArticleScience advances2021
Low-flow intussusception and metastable VEGFR2 signaling launch angiogenesis in ischemic muscle.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Pro-Angiogenic Bioactive Molecules in Vascular Morphogenesis: Integrating Endothelial Cell Dynamics.Current issues in molecular biology · 2025Review
- Reversal of cerebrovascular anomalies in a zebrafish model of vein of Galen aneurysm.Nature cardiovascular research · 2025Article
- Intussusceptive angiogenesis-on-a-chip: Evidence for transluminal vascular bridging by endothelial delamination.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Inducible deletion of endothelial cell Efnb2 delays capillary regeneration and attenuates myofibre reinnervation following myotoxin injury in mice.The Journal of physiology · 2024Article
- Endothelial cells signaling and patterning under hypoxia: a mechanistic integrative computational model including the Notch-Dll4 pathway.Frontiers in physiology · 2024Article
- Transluminal Pillars-Their Origin and Role in the Remodelling of the Zebrafish Caudal Vein Plexus.International journal of molecular sciences · 2023Article
- Capillary Dynamics Regulate Post-Ischemic Muscle Damage and Regeneration in Experimental Hindlimb Ischemia.Cells · 2023Article
- Endothelial cells signaling and patterning under hypoxia: a mechanistic integrative computational model including the Notch-Dll4 pathway.bioRxiv : the preprint server for biology · 2023Article
- Angiogenic Microvascular Wall Shear Stress Patterns Revealed Through Three-dimensional Red Blood Cell Resolved Modeling.Function (Oxford, England) · 2023Article
- AAV-mediated expression of PFKFB3 in myofibers, but not endothelial cells, improves ischemic muscle function in mice with critical limb ischemia.American journal of physiology. Heart and circulatory physiology · 2022Article
- Replacement in angiogenesis research: Studying mechanisms of blood vessel development by animal-freeFrontiers in physiology · 2022Review
Corrections and comments
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Authors and funding
19 authors.
Funding
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Abstract
Efforts to promote sprouting angiogenesis in skeletal muscles of individuals with peripheral artery disease have not been clinically successful. We discovered that, contrary to the prevailing view, angiogenesis following ischemic muscle injury in mice was not driven by endothelial sprouting. Instead, real-time imaging revealed the emergence of wide-caliber, primordial conduits with ultralow flow that rapidly transformed into a hierarchical neocirculation by transluminal bridging and intussusception. This process was accelerated by inhibiting vascular endothelial growth factor receptor-2 (VEGFR2). We probed this response by developing the first live-cell model of transluminal endothelial bridging using microfluidics. Endothelial cells subjected to ultralow shear stress could reposition inside the flowing lumen as pillars. Moreover, the low-flow lumen proved to be a privileged location for endothelial cells with reduced VEGFR2 signaling capacity, as VEGFR2 mechanosignals were boosted. These findings redefine regenerative angiogenesis in muscle as an intussusceptive process and uncover a basis for its launch.
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Registered trials
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