Vascular adaptation to a dysfunctional endothelium as a consequence of Shb deficiency.

Angiogenesis
Gustaf ChristofferssonMichael Welsh

Abstract

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 μm 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 Matrigel™ 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 mea...Continue Reading

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Citations

Oct 23, 2015·Journal of Molecular Endocrinology·Michael WelshBjörn Åkerblom
Dec 12, 2012·Journal of Internal Medicine·L Claesson-Welsh, M Welsh
Oct 21, 2016·Redox Biology·Shuai YuanChristopher G Kevil
Oct 7, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Maria JamalpourMichael Welsh
May 23, 2020·International Journal of Cancer. Journal International Du Cancer·Qi HeMichael Welsh

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