Tie2 as a novel key factor of microangiopathy in systemic sclerosis

dc.contributor.authorMoritz, Falk
dc.contributor.authorSchniering, Janine
dc.contributor.authorDistler, Jörg H. W.
dc.contributor.authorGay, Renate E.
dc.contributor.authorGay, Steffen
dc.contributor.authorDistler, Oliver
dc.contributor.authorMaurer, Britta
dc.date.accessioned2017-07-03
dc.date.available2017-05-29
dc.date.created2017
dc.date.issued2017-07-03
dc.description.abstractBackground The angiopoietin(Ang)/Tie2 system is a key regulator of vascular biology. The expression of membrane bound (mb) Tie2 and Ang-1 ensures vessel stability, whereas Ang-2, inducible by vascular endothelial growth factor (VEGF), hypoxia, and inflammation, acts as an antagonist. Tie2 signalling is also attenuated by soluble Tie2 (sTie2), the extracellular domain of the receptor, which is shed upon stimulation with VEGF. Herein, we investigate the role of Ang/Tie2 in the peripheral vasculopathy in systemic sclerosis (SSc) including animal models. Methods The expression of Ang-1/-2 and Tie2 in skin/serum of SSc patients was compared with healthy controls by immunohistochemistry (IHC)/ELISA. Expression of Ang/Tie2 was analysed in different animal models: VEGF transgenic (tg) mice, hypoxia model, bleomycin-induced skin fibrosis, and tight skin 1 (TSK1) mice. Results In SSc, dermal microvessels abundantly expressed Ang-2, but not Ang-1 compared with healthy controls. The percentage of mbTie2+ microvessels was profoundly decreased whereas the levels of sTie2 were increased already in early disease. Both in skin and sera of SSc patients, the Ang1/2 ratio was reduced, being lowest in patients with digital ulcers indicating vessel destabilizing conditions. We next studied potential influencing factors in animal models. The VEGF tg mouse model, the hypoxia, and the inflammation-dependent bleomycin model all showed a similar dysregulation of Ang/Tie2 as in SSc, which did not apply for the non-inflammatory TSK1 model. Conclusion Peripheral microvasculopathy in SSc results from a complex dysregulation of angiogenic signalling networks including the VEGF and the Ang/Tie2 system. The profoundly disturbed Ang-/Tie-2 balance might represent an important target for vascular therapeutic approaches in SSc.en
dc.identifier.citationArthritis Research & Therapy 19 (2017). <https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-017-1304-2>
dc.identifier.doihttps://doi.org/10.1186/s13075-017-1304-2
dc.identifier.opus-id8543
dc.identifier.urihttps://open.fau.de/handle/openfau/8543
dc.identifier.urnurn:nbn:de:bvb:29-opus4-85430
dc.language.isoen
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/de/deed.de
dc.subjectMicrovasculopathy
dc.subjectSystemic sclerosis
dc.subjectAngiopoietins
dc.subjectTie2
dc.subject.ddcDDC Classification::6 Technik, Medizin, angewandte Wissenschaften :: 61 Medizin und Gesundheit :: 610 Medizin und Gesundheit
dc.titleTie2 as a novel key factor of microangiopathy in systemic sclerosisen
dc.typearticle
dcterms.publisherFriedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
local.journal.titleArthritis Research & Therapy
local.journal.volume19
local.sendToDnbfree*
local.subject.fakultaetMedizinische Fakultät
local.subject.gnd-
local.subject.sammlungUniversität Erlangen-Nürnberg / Open Access Artikel ohne Förderung / Open Access Artikel ohne Förderung 2017
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