scholarly journals The Many Faces of Interleukin-6: The Role of IL-6 in Inflammation, Vasculopathy, and Fibrosis in Systemic Sclerosis

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Theresa C. Barnes ◽  
Marina E. Anderson ◽  
Robert J. Moots
Keyword(s):  
Systemic Sclerosis ◽  
Endothelial Cell ◽  
Interleukin 6 ◽  
Signalling Pathways ◽  
Endothelial Cell Dysfunction ◽  
Potential Therapeutic Target ◽  
Cell Dysfunction ◽  
Significant Interest ◽  
The Many

Interleukin-6 is currently attracting significant interest as a potential therapeutic target in systemic sclerosis (SSc). In this paper, the biology of interleukin-6 is reviewed, and the evidence for interleukin-6 dysregulation in SSc is explored. The role of inteleukin-6 classical and trans signalling pathways in SSc relevant phenomena such as chronic inflammation, autoimmunity, endothelial cell dysfunction, and fibrogenesis is discussed. The existing evidence that interventions designed to block interleukin-6 signalling are of therapeutic relevance in SSc is evaluated.

Role of glutathione redox cycle in TNF-α-mediated endothelial cell dysfunction

1995 ◽  
Vol 117 (2) ◽  
pp. 179-188 ◽  
Author(s):  
Michal Toborek ◽  
Steven W. Barger ◽  
Mark P. Mattson ◽  
Craig J. McClain ◽  
Bernhard Hennig
Keyword(s):  
Endothelial Cell ◽  
Redox Cycle ◽  
Endothelial Cell Dysfunction ◽  
Cell Dysfunction ◽  
Glutathione Redox Cycle ◽  
Tnf Α ◽  
Glutathione Redox

Role of Insulin and Adenosine in the Human Placenta Microvascular and Macrovascular Endothelial Cell Dysfunction in Gestational Diabetes Mellitus

2014 ◽  
Vol 21 (1) ◽  
pp. 26-37 ◽  
Author(s):  
Enrique Guzmán-Gutiérrez ◽  
Pablo Arroyo ◽  
Rocío Salsoso ◽  
Bárbara Fuenzalida ◽  
Tamara Sáez ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Endothelial Cell ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Human Placenta ◽  
Endothelial Cell Dysfunction ◽  
Cell Dysfunction

scholarly journals Critical Role of Mortalin/GRP75 In Endothelial Cell Dysfunction Associated With Acute Lung Injury

Shock ◽  
2019 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Antony Leonard ◽  
Pei Yi Su ◽  
David I. Yule ◽  
Arshad Rahman ◽  
Fabeha Fazal
Keyword(s):  
Acute Lung Injury ◽  
Endothelial Cell ◽  
Lung Injury ◽  
Critical Role ◽  
Endothelial Cell Dysfunction ◽  
Cell Dysfunction

Role of activin A in the pathogenesis of endothelial cell dysfunction in preeclampsia

2016 ◽  
Vol 6 (2) ◽  
pp. 130-133 ◽  
Author(s):  
Sebastian R. Hobson ◽  
Rutu Acharya ◽  
Rebecca Lim ◽  
Siow Teng Chan ◽  
Joanne Mockler ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Activin A ◽  
Endothelial Cell Dysfunction ◽  
Cell Dysfunction

scholarly journals Contribution to The Peripheral Vasculopathy and Endothelial Cell Dysfunction by CXCL4 in Systemic Sclerosis

2020 ◽  
Author(s):  
Zhixing Jiang ◽  
Chen Chen ◽  
Lingbiao Wang ◽  
Xiaoxia Zhu ◽  
Yu Xue ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Systemic Sclerosis ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Umbilical Vein ◽  
Digital Ulcers ◽  
Healthy Controls ◽  
Endothelial Cell Dysfunction ◽  
Cell Dysfunction

Abstract Objective CXCL4, a chemokine with antiangiogenic property, is reported to be involved in systemic sclerosis (SSc) related pulmonary arterial hypertension (PAH). We investigated the contribution of CXCL4 to SSc development by focusing on the correlation of circulatory CXCL4 levels with their peripheral vasculopathy, as well as the effect of CXCL4 on endothelial cell dysfunction and angiogenesis disturbance in SSc and the potential signaling.Methods We measured the serum CXCL4 levels in 58 patients with SSc, 10 patients with the very early diagnosis of SSc (VEDOSS), and 80 healthy controls. Then, CXCL4 levels were correlated with their clinical features, especially the peripheral vasculopathy. These observations were further validated in an additional cohort including 50 SSc patients, 12 VEDOSS patients, and 80 healthy controls. Moreover, we studied the anti-angiogenesis effects and the underlying signaling of CXCL4 in human umbilical vein endothelial cells (HUVECs) in vitro. Results Circulating levels of the CXCL4 were 103.62% higher in patients with SSc and 201.51 % higher in patients with VEDOSS than matched HCs, and these observations were confirmed in two independent cohorts. CXCL4 levels were closely associated with digital ulcers (DU) and nailfold video capillaroscopy (NVC) abnormalities in SSc. The proliferation, migration, and tube formation of HUVECs were significantly inhibited by recombinant human CXCL4 or SSc derived serum, which reversed by CXCL4 neutralizing antibody, but not CXCR3 inhibitor. CXCL4 downregulated the transcription factor Friend leukaemia integration factor‐1 (Fli-1) via c-Abl signaling. Furthermore, CXCL4 blocked the transforming growth factor (TGF) -β or platelet-derived growth factor (PDGF) induced cell proliferation of HUVECs. Conclusions CXCL4 may contribute to peripheral vasculopathy in SSc by downregulating Fli-1 via c-Abl signaling in endothelial cells and interfering angiogenesis.

Role of Activin A in the Pathogenesis of Endothelial Cell Dysfunction in Preeclampsia

2017 ◽  
pp. 39-52
Author(s):  
Sebastian R. Hobson ◽  
Rebecca Lim ◽  
Joanne C. Mockler ◽  
Seshini Gurusinghe ◽  
Euan M. Wallace
Keyword(s):  
Endothelial Cell ◽  
Activin A ◽  
Endothelial Cell Dysfunction ◽  
Cell Dysfunction

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

2018 ◽  
Vol 77 (11) ◽  
pp. 1665-1674 ◽  
Author(s):  
Eloisa Romano ◽  
Mirko Manetti ◽  
Irene Rosa ◽  
Bianca Saveria Fioretto ◽  
Lidia Ibba-Manneschi ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Endothelial Cell ◽  
Tube Formation ◽  
Endothelial Cell Dysfunction ◽  
Cell Dysfunction ◽  
Robo Receptors ◽  
Skin Biopsies ◽  
Kinase Phosphorylation ◽  
Guidance Molecule

ObjectiveIn 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.MethodsCirculating 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.ResultsCirculating 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 inhibitory effects were significantly attenuated when SSc sera were preincubated with an anti-Slit2 blocking antibody. In vitro angiogenesis was severely compromised in SSc-MVECs and could be significantly ameliorated by Slit2 neutralisation or ROBO4 gene silencing. Slit2/Robo4 axis interfered with angiogenesis through the inhibition of Src kinase phosphorylation.ConclusionsIn SSc, increased circulating levels of Slit2 and activation of the Slit2/Robo4 antiangiogenic axis may contribute to peripheral microangiopathy since the very early phase of the disease.

scholarly journals Role of Connexin40 in Coronary Endothelial Cell Dysfunction in Type 1 Diabetic Mice

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Ayako Makino ◽  
Oleksandr Platoshyn ◽  
Jorge Suarez ◽  
Jason X.‐J. Yuan ◽  
Wolfgang H. Dillmann
Keyword(s):  
Endothelial Cell ◽  
Endothelial Cell Dysfunction ◽  
Diabetic Mice ◽  
Cell Dysfunction
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