ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2015
Angiopoietin-4 increases permeability of blood vessels and promotes lymphatic dilation.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Dynamic Remodeling of Oocyte-Granulosa Cell Communication During Bovine Folliculogenesis Revealed by Transcriptomic Meta-Analyses.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Pooled it
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- Angiopoietin-4 expression and potential mechanisms in carcinogenesis: Current achievements and perspectives.Clinical and experimental medicine · 2024Review
- ANGPTL4 regulates ovarian cancer progression by activating the ERK1/2 pathway.Cancer cell international · 2024Article
- Angiopoietin4 (ANGPT4) expression and potential mechanisms in carcinogenesis: current achievements and perspectives.Clinical and experimental medicine · 2023Review
- Single-cell analysis reveals an Angpt4-initiated EPDC-EC-CM cellular coordination cascade during heart regeneration.Protein & cell · 2023Article
- Visualizing vasculature and its response to therapy in the tumor microenvironment.Theranostics · 2023Review
- A bioengineered lymphatic vessel model for studying lymphatic endothelial cell-cell junction and barrier function.Microcirculation (New York, N.Y. : 1994) · 2021Article
- Synergetic responses of intestinal microbiota and epithelium to dietary inulin supplementation in pigs.European journal of nutrition · 2021Article
- Updates on the molecular genetics of primary congenital glaucoma (Review).Experimental and therapeutic medicine · 2020Review
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- Gene expression in retinal ischemic post-conditioning.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2018Article
- The Lymphatic System in Disease Processes and Cancer Progression.Annual review of biomedical engineering · 2016Review
- Measuring Vascular Permeability In Vivo.Methods in molecular biology (Clifton, N.J.) · 2016Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The angiopoietin (Ang) ligands are potential therapeutic targets for lymphatic related diseases, which include lymphedema and cancer. Ang-1 and Ang-2 functions are established, but those of Ang-4 are poorly understood. We used intravital fluorescence microscopy to characterize Ang-4 actions on T241 murine fibrosarcoma-associated vessels in mice. The diameters of lymphatic vessels draining Ang-4- or VEGF-C (positive control)-expressing tumors increased to 123 and 135 μm, respectively, and parental, mock-transduced (negative controls) and tumors expressing Ang-1 or Ang-2 remained at baseline (∼60 μm). Ang-4 decreased human dermal lymphatic endothelial cell (LEC) monolayer permeability by 27% while increasing human dermal blood endothelial cell (BEC) monolayer permeability by 200%. In vivo, Ang-4 stimulated a 4.5-fold increase in tumor-associated blood vessel permeability compared with control when measured using intravital quantitative multiphoton microscopy. Ang-4 activated receptor signaling in both LECs and BECs, evidenced by tyrosine kinase with Ig and endothelial growth factor homology domains-2 (TIE2) receptor, protein kinase B, and Erk1,2 phosphorylation detectable by immunoblotting. These data suggest that Ang-4 actions are mediated through cell-type-specific networks and that lymphatic vessel dilation occurs secondarily to increased vascular leakage. Ang-4 also promoted survival of LECs. Thus, blocking Ang-4 may prune the draining lymphatic vasculature and decrease interstitial fluid pressure (IFP) by reducing vascular permeability.
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Registered trials
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