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Factors regulating capillary remodeling in a reversible model of inflammatory corneal angiogenesis
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.ORCID iD: 0000-0001-8722-9155
Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
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2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, 1-15 p., 32137Article in journal (Refereed) Published
Abstract [en]

Newly formed microcapillary networks arising in adult organisms by angiogenic and inflammatory stimuli contribute to pathologies such as corneal and retinal blindness, tumor growth, and metastasis. Therapeutic inhibition of pathologic angiogenesis has focused on targeting the VEGF pathway, while comparatively little attention has been given to remodeling of the new microcapillaries into a stabilized, functional, and persistent vascular network. Here, we used a novel reversible model of inflammatory angiogenesis in the rat cornea to investigate endogenous factors rapidly invoked to remodel, normalize and regress microcapillaries as part of the natural response to regain corneal avascularity. Rapid reversal of an inflammatory angiogenic stimulus suppressed granulocytic activity, enhanced recruitment of remodelling macrophages, induced capillary intussusception, and enriched pathways and processes involving immune cells, chemokines, morphogenesis, axonal guidance, and cell motility, adhesion, and cytoskeletal functions. Whole transcriptome gene expression analysis revealed suppression of numerous inflammatory and angiogenic factors and enhancement of endogenous inhibitors. Many of the identified genes function independently of VEGF and represent potentially new targets for molecular control of the critical process of microvascular remodeling and regression in the cornea.

Place, publisher, year, edition, pages
Nature Publishing Group, 2016. Vol. 6, 1-15 p., 32137
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Cell and Molecular Biology
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URN: urn:nbn:se:liu:diva-131501DOI: 10.1038/srep32137ISI: 000381967600002PubMedID: 27561355OAI: oai:DiVA.org:liu-131501DiVA: diva2:974466
Note

Funding Agencies|Bayer HealthCare AB, Solna, Sweden; Swedish Research Council [2012-2472]

Available from: 2016-09-26 Created: 2016-09-23 Last updated: 2016-10-19Bibliographically approved

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Mukwaya, AnthonnyPeebo, BeatriceXeroudaki, MariaAli, ZaheerLennikov, AntonJensen, LasseLagali, Neil
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Division of Neuro and Inflammation ScienceFaculty of Medicine and Health SciencesDepartment of Ophthalmology in LinköpingDivision of Cardiovascular MedicineDepartment of Clinical Pharmacology
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