Slit2/Robo4 axis may contribute to endothelial cell dysfunction and angiogenesis disturbance in systemic sclerosis

Annals of the Rheumatic Diseases
Eloisa RomanoSerena Guiducci

Abstract

In systemic sclerosis (SSc), early microvascular injury is followed by impaired angiogenesis and peripheral capillary loss. Here, we investigated the possible contribution of the neurovascular guidance molecule Slit2 and its Roundabout (Robo) receptors to SSc-related endothelial cell dysfunction. Circulating Slit2 levels were measured in patients with SSc and healthy controls. Slit2, Robo1 and Robo4 expression was investigated in SSc and healthy skin biopsies and explanted dermal microvascular endothelial cells (MVECs). Slit2/Robo4 function in MVEC angiogenesis was studied by cell viability, wound healing and capillary-like tube formation assays. Circulating Slit2 was significantly increased in either SSc or patients with a very early diagnosis of SSc (VEDOSS) compared with controls. Interestingly, serum Slit2 levels were raised in patients with VEDOSS with nailfold videocapillaroscopy (NVC) abnormalities, while they were similar in VEDOSS with normal NVC and controls. In SSc, Slit2 and Robo4 expression was upregulated in clinically affected skin and explanted MVECs in respect to controls. The angiogenic performance of healthy MVECs was significantly reduced after challenge with recombinant human Slit2 or SSc sera. These inhibi...Continue Reading

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Citations

Mar 3, 2019·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Tam T T PhuongLisa A Lesniewski
Jun 5, 2019·Bioscience Reports·Chang DaiGuanfang Su
Dec 11, 2019·International Journal of Molecular Sciences·Mirko ManettiMarco Matucci-Cerinic
Oct 21, 2020·Clinical and Experimental Medicine·Yi ZhangXuyan Yang
Jan 11, 2021·Translational Research : the Journal of Laboratory and Clinical Medicine·Fabian A MendozaSergio A Jimenez

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