The growth factor effect on endothelial cell dysfunction in the presence of glycated collagen and A[beta] peptide : implications for decreased angiogenesis in diabetes and Alzheimer's disease

2021 ◽  
Author(s):  
Justin George Mathew
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Endothelial Cell Dysfunction ◽  
Cell Dysfunction ◽  
Factor Effect ◽  
Beta Peptide

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.

scholarly journals Contribution to the peripheral vasculopathy and endothelial cell dysfunction by CXCL4 in Systemic Sclerosis

2020 ◽  
Author(s):  
Zhixing Jiang ◽  
Chen Chen ◽  
Sen Yang ◽  
Hang He ◽  
Xiaoxia Zhu ◽  
...  
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.MethodsWe 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. ResultsCirculating 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.

scholarly journals Vascular adaptation in pregnancy and endothelial dysfunction in preeclampsia

2017 ◽  
Vol 232 (1) ◽  
pp. R27-R44 ◽  
Author(s):  
D S Boeldt ◽  
I M Bird
Keyword(s):  
Endothelial Cell ◽  
Endothelial Dysfunction ◽  
Cell Function ◽  
Endothelial Cell Dysfunction ◽  
Hypertensive Disorders Of Pregnancy ◽  
Endothelial Cell Function ◽  
Vascular Adaptation ◽  
Cell Dysfunction ◽  
Maternal Adaptation ◽  
Flow Through

Maternal vascular adaptation to pregnancy is critically important to expand the capacity for blood flow through the uteroplacental unit to meet the needs of the developing fetus. Failure of the maternal vasculature to properly adapt can result in hypertensive disorders of pregnancy such as preeclampsia (PE). Herein, we review the endocrinology of maternal adaptation to pregnancy and contrast this with that of PE. Our focus is specifically on those hormones that directly influence endothelial cell function and dysfunction, as endothelial cell dysfunction is a hallmark of PE. A variety of growth factors and cytokines are present in normal vascular adaptation to pregnancy. However, they have also been shown to be circulating at abnormal levels in PE pregnancies. Many of these factors promote endothelial dysfunction when present at abnormal levels by acutely inhibiting key Ca2+ signaling events and chronically promoting the breakdown of endothelial cell–cell contacts. Increasingly, our understanding of how the contributions of the placenta, immune cells, and the endothelium itself promote the endocrine milieu of PE is becoming clearer. We then describe in detail how the complex endocrine environment of PE affects endothelial cell function, why this has contributed to the difficulty in fully understanding and treating this disorder, and how a focus on signaling convergence points of many hormones may be a more successful treatment strategy.

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
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