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Vascular adaptation to a dysfunctional endothelium as a consequence of Shb deficiency
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
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2012 (English)In: Angiogenesis, ISSN 0969-6970, E-ISSN 1573-7209, Vol. 15, no 3, 469-480 p.Article in journal (Refereed) Published
Abstract [en]

Vascular endothelial growth factor (VEGF)-A regulates angiogenesis, vascular morphology and permeability by signaling through its receptor VEGFR-2. The Shb adapter protein has previously been found to relay certain VEGFR-2 dependent signals and consequently vascular physiology and structure was assessed in Shb knockout mice. X-ray computed tomography of vessels larger than 24 mm diameter (micro-CT) after contrast injection revealed an increased frequency of 48-96 µm arterioles in the hindlimb calf muscle in Shb knockout mice. Intravital microscopy of the cremaster muscle demonstrated a less regular vasculature with fewer branch points and increased vessel tortuosity, changes that led to an increased blood flow velocity. Reduced in vivo angiogenesis was observed in Shb knockout MatrigelTM plugs. Unlike the wild-type situation, VEGF-A did not provoke a dissociation of VE-cadherin from adherens junctions in Shb knockout venules. The reduced angiogenesis and altered properties of junctions had consequences for two patho-physiological responses to arterial occlusion: vascular permeability was reduced in the Shb knockout cremaster muscle after ligation of one supplying artery and heat-induced blood flow determined by Laser-Doppler measurements was decreased in the hindlimb after ligation of the femoral artery. Consequently, the Shb knockout mouse exhibited structural and functional (angiogenesis and vascular permeability) vascular abnormalities that have implications for understanding the function of VEGF-A under physiological conditions.

Place, publisher, year, edition, pages
2012. Vol. 15, no 3, 469-480 p.
Keyword [en]
VEGF, VE-cadherin, adherens junctions and permeability, angiogenesis, Src homology-2 protein B, blood flow
National Category
Medical and Health Sciences
Research subject
Medical Cell Biology
Identifiers
URN: urn:nbn:se:uu:diva-173446DOI: 10.1007/s10456-012-9275-zISI: 000307272200012OAI: oai:DiVA.org:uu-173446DiVA: diva2:517671
Funder
Swedish Research Council, K2011-54X-10822-18-6
Available from: 2012-04-27 Created: 2012-04-24 Last updated: 2017-12-07Bibliographically approved

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Christoffersson, GustavZang, GuangxiangVågesjö, EvelinaPhillipson, MiaWelsh, Michael
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Integrative PhysiologyDepartment of Medical Cell Biology
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