ArticleEMBO molecular medicine2015
VEGF dose regulates vascular stabilization through Semaphorin3A and the Neuropilin-1+ monocyte/TGF-β1 paracrine axis.
Article in EMBO molecular medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- Reduced vascular leakage correlates with breast carcinoma T regulatory cell infiltration but not with metastatic propensity.Molecular oncology · 2026Article
- Cell communication and relevant signaling pathways in osteogenesis-angiogenesis coupling.Bone research · 2025Review
- Bioengineering methods for vascularizing organoids.Cell reports methods · 2024Review
- Semaphorin 3A promotes the long-term persistence of human SVF-derived microvascular networks in engineered grafts.Frontiers in bioengineering and biotechnology · 2024Article
- Enhanced angiogenic properties of umbilical cord blood primed by OP9 stromal cells ameliorates neurological deficits in cerebral infarction mouse model.Scientific reports · 2023Article
- Fibrin-based factor delivery for therapeutic angiogenesis: friend or foe?Cell and tissue research · 2022Review
- Fetal Blood Flow and Genetic Mutations in Conotruncal Congenital Heart Disease.Journal of cardiovascular development and disease · 2021Review
- The Prognostic Value of Serum Semaphorin3A and VEGF Levels in Patients with Metastatic Colorectal Cancer.Journal of gastrointestinal cancer · 2020Article
- Therapeutic vascularization in regenerative medicine.Stem cells translational medicine · 2020Review
- Type H blood vessels in bone modeling and remodeling.Theranostics · 2020Review
- TGF-β-Mediated Epithelial-Mesenchymal Transition and Cancer Metastasis.International journal of molecular sciences · 2019Review
- EphrinB2/EphB4 signaling regulates non-sprouting angiogenesis by VEGF.EMBO reports · 2018Article
- Myocardial infarction stabilization by cell-based expression of controlled Vascular Endothelial Growth Factor levels.Journal of cellular and molecular medicine · 2018Article
- A mechanism for semaphorin-induced apoptosis: DNA damage of endothelial and myogenic cells in primary cultures from skeletal muscle.Oncotarget · 2018Article
- VEGF nanoparticles repair the heart after myocardial infarction.American journal of physiology. Heart and circulatory physiology · 2018Article
- Retinal Vascular Degeneration in the Transgenic P23H Rat Model of Retinitis Pigmentosa.Frontiers in neuroanatomy · 2018Article
- Gelatin device for the delivery of growth factors involved in endochondral ossification.PloS one · 2017Article
- It Takes Two to Tango: Coupling of Angiogenesis and Osteogenesis for Bone Regeneration.Frontiers in bioengineering and biotechnology · 2017Review
- Platelet-Rich Plasma as an Autologous and Proangiogenic Cell Delivery System.Mediators of inflammation · 2017Article
- Long-term safety and stability of angiogenesis induced by balanced single-vector co-expression of PDGF-BB and VEGF164 in skeletal muscle.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
VEGF is widely investigated for therapeutic angiogenesis, but while short-term delivery is desirable for safety, it is insufficient for new vessel persistence, jeopardizing efficacy. Here, we investigated whether and how VEGF dose regulates nascent vessel stabilization, to identify novel therapeutic targets. Monoclonal populations of transduced myoblasts were used to homogeneously express specific VEGF doses in SCID mouse muscles. VEGF was abrogated after 10 and 17 days by Aflibercept treatment. Vascular stabilization was fastest with low VEGF, but delayed or prevented by higher doses, without affecting pericyte coverage. Rather, VEGF dose-dependently inhibited endothelial Semaphorin3A expression, thereby impairing recruitment of Neuropilin-1-expressing monocytes (NEM), TGF-β1 production and endothelial SMAD2/3 activation. TGF-β1 further initiated a feedback loop stimulating endothelial Semaphorin3A expression, thereby amplifying the stabilizing signals. Blocking experiments showed that NEM recruitment required endogenous Semaphorin3A and that TGF-β1 was necessary to start the Semaphorin3A/NEM axis. Conversely, Semaphorin3A treatment promoted NEM recruitment and vessel stabilization despite high VEGF doses or transient adenoviral delivery. Therefore, VEGF inhibits the endothelial Semaphorin3A/NEM/TGF-β1 paracrine axis and Semaphorin3A treatment accelerates stabilization of VEGF-induced angiogenesis.
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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.