ArticleArteriosclerosis, thrombosis, and vascular biology2014
Genetic reduction of vascular endothelial growth factor receptor 2 rescues aberrant angiogenesis caused by epsin deficiency.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 48 citations in OpenAlex.
- Endocytic Adaptor Proteins in Vascular Diseases: Critical Role of Intracellular Trafficking in Regulating Pathobiology of Vascular Disorders.Cardiology discovery · 2026Review
- Single-Cell Analysis Reveals a Critical Role for Macrophage Epsins in Regulating the Origin of Foam Cells in Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Elucidating the crosstalk between endothelial-to-mesenchymal transition (EndoMT) and endothelial autophagy in the pathogenesis of atherosclerosis.Vascular pharmacology · 2024Review
- Epsin Endocytic Adaptor Proteins in Angiogenic and Lymphangiogenic Signaling.Cold Spring Harbor perspectives in medicine · 2024Review
- Article
- Epsin Nanotherapy Regulates Cholesterol Transport to Fortify Atheroma Regression.Circulation research · 2023Article
- Endothelial FGF signaling is protective in hypoxia-induced pulmonary hypertension.The Journal of clinical investigation · 2021Article
- Epsins Negatively Regulate Aortic Endothelial Cell Function by Augmenting Inflammatory Signaling.Cells · 2021Article
- Effects of exercise training with weight loss on skeletal muscle expression of angiogenic factors in overweight and obese older men.Journal of applied physiology (Bethesda, Md. : 1985) · 2021Article
- The P-type ATPase transporter ATP7A promotes angiogenesis by limiting autophagic degradation of VEGFR2.Nature communications · 2021Article
- Article
- Tubulin carboxypeptidase activity of vasohibin-1 inhibits angiogenesis by interfering with endocytosis and trafficking of pro-angiogenic factor receptors.Angiogenesis · 2021Article
- Epsins in vascular development, function and disease.Cellular and molecular life sciences : CMLS · 2021Review
- Epsins 1 and 2 promote NEMO linear ubiquitination via LUBAC to drive breast cancer development.The Journal of clinical investigation · 2021Article
- Epsin-mediated degradation of IP3R1 fuels atherosclerosis.Nature communications · 2020Article
- Genes and Pathways Implicated in Tetralogy of Fallot Revealed by Ultra-Rare Variant Burden Analysis in 231 Genome Sequences.Frontiers in genetics · 2020Article
- Endocytic Adaptors in Cardiovascular Disease.Frontiers in cell and developmental biology · 2020Review
- Endocytic Adaptor Proteins in Health and Disease: Lessons from Model Organisms and Human Mutations.Cells · 2019Review
- Endophilin-A2 dependent VEGFR2 endocytosis promotes sprouting angiogenesis.Nature communications · 2019Article
- Review
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
objectiveWe previously showed that endothelial epsin deficiency caused elevated vascular endothelial growth factor receptor 2 (VEGFR2) and enhanced VEGF signaling, resulting in aberrant tumor angiogenesis and reduced tumor growth in adult mice. However, direct evidence demonstrating that endothelial epsins regulate angiogenesis specifically through VEGFR2 downregulation is still lacking. In addition, whether the lack of epsins causes abnormal angiogenesis during embryonic development remains unclear. APPROACH AND
resultsA novel strain of endothelial epsin-deleted mice that are heterozygous for VEGFR2 (Epn1(fl/fl); Epn2(-/-); Flk(fl/+); iCDH5 Cre mice) was created. Analysis of embryos at different developmental stages showed that deletion of epsins caused defective embryonic angiogenesis and retarded embryo development. In vitro angiogenesis assays using isolated primary endothelial cells (ECs) from Epn1(fl/fl); Epn2(-/-); iCDH5 Cre (EC-iDKO) and Epn1(fl/fl); Epn2(-/-); Flk(fl/+); iCDH5 Cre (EC-iDKO-Flk(fl/+)) mice demonstrated that VEGFR2 reduction in epsin-depleted cells was sufficient to restore normal VEGF signaling, EC proliferation, EC migration, and EC network formation. These findings were complemented by in vivo wound healing, inflammatory angiogenesis, and tumor angiogenesis assays in which reduction of VEGFR2 was sufficient to rescue abnormal angiogenesis in endothelial epsin-deleted mice.
conclusionsOur results provide the first genetic demonstration that epsins function specifically to downregulate VEGFR2 by mediating activated VEGFR2 internalization and degradation and that genetic reduction of VEGFR2 level protects against excessive angiogenesis caused by epsin loss. Our findings indicate that epsins may be a potential therapeutic target in conditions in which tightly regulated angiogenesis is crucial, such as in diabetic wound healing and tumors.
Indexed as
Identifiers
What OpenQuestion holds
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.