VEGF-C mediates cyclic pressure-induced endothelial cell proliferation

2002 ◽  
Vol 11 (3) ◽  
pp. 245-251 ◽  
Author(s):  
Hainsworth Y. Shin ◽  
Michael L. Smith ◽  
Karen J. Toy ◽  
P. Mickey Williams ◽  
Rena Bizios ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Growth Factor ◽  
Gene Transcription ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Umbilical Vein ◽  
Culture Conditions ◽  
Endothelial Cell Proliferation ◽  
Cyclic Pressure ◽  
Cell Functions

Mechanical forces modulate endothelial cell functions through several mechanisms including regulation of gene transcription. In the present study, gene transcription by human umbilical vein endothelial cells (HUVEC) either maintained under control pressure (that is, standard cell culture conditions equivalent to 0.15 mmHg sustained hydrostatic pressure) or exposed to 60/20 mmHg sinusoidal pressures at 1 Hz were compared using Affymetrix GeneChip microarrays to identify cellular/molecular mechanisms associated with endothelial cell responses to cyclic pressure. Cyclic pressure selectively affected transcription of 14 genes that included a set of mechanosensitive proteins involved in hemostasis (tissue plasminogen activator), cell adhesion (integrin-α2), and cell signaling (Rho B, cytosolic phospholipase A2), as well as a unique subset of cyclic pressure-sensitive genes such as vascular endothelial growth factor (VEGF)-C and transforming growth factor (TGF)-β2. The present study also provided first evidence that VEGF-C, the most highly induced gene under 60/20 mmHg, mediated HUVEC proliferation in response to this cyclic pressure. Cyclic pressure is, therefore, a mechanical force that modulates endothelial cell functions (such as proliferation) by activating a specific transcriptional program.

scholarly journals miR-27b Suppresses Endothelial Cell Proliferation and Migration by Targeting Smad7 in Kawasaki Disease

2018 ◽  
Vol 48 (4) ◽  
pp. 1804-1814 ◽  
Author(s):  
Xing Rong ◽  
Donghui Ge ◽  
Danping Shen ◽  
Xianda Chen ◽  
Xuliang Wang ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Kawasaki Disease ◽  
Therapeutic Target ◽  
Umbilical Vein ◽  
Luciferase Reporter ◽  
Endothelial Cell Proliferation ◽  
Cell Functions ◽  
Potential Biomarker ◽  
And Migration ◽  
Proliferation And Migration

Background/Aims: Increasing evidence indicates that microRNAs (miRNAs) play important roles in Kawasaki disease (KD). Our previous study demonstrated that hsa-miR-27b-3p (miR-27b) was up-regulated in KD serum. However, the specific role of miR-27b in KD remains unclear. We aimed to investigate that miR-27b could be a biomarker and therapeutic target for KD treatment. As well, the specific mechanism of miR-27b effecting endothelial cell functions was studied. Methods: The expression of miR-27b and Smad7 was measured by qRT-PCR. Gain-of-function strategy was used to observe the effect of miR-27b on human umbilical vein endothelial cells (HUVECs) proliferation and migration. Bioinformatics analyses were applied to predict miR-27b targets and then we verified Smad7 by a luciferase reporter assay. Western blot was performed to detect the protein expression of Smad7, PCNA, MMP9, MMP12 and TGF-β-related genes. Results: We confirmed that miR-27b was shown to be dramatically up-regulated in KD serum and KD serum-treated HUVECs and that elevated expression of miR-27b suppressed the proliferation and migration of HUVECs. Furthermore, our results verified that miR-27b mediated cell functions by affecting the TGF-β via targeting Smad7 in HUVECs. Conclusion: These results suggested that up-regulated miR-27b had a protective role in HUVECs proliferation and migration via targeting Smad7 and affecting TGF-β pathway. Therefore, miR-27b represented a potential biomarker for KD and may serve as a promising therapeutic target for KD treatment.

MODULATION of PROSTACYCLIN PRODUCTION BY HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS WITH ECGF/HEPARIN MEDIUM : ROLE OF CELLULAR DENSITY AT CONFLUENCE

1987 ◽  
Author(s):  
O BOUTHERIN-FALSON ◽  
N BLAES
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Umbilical Vein ◽  
Calf Serum ◽  
Lower Amount ◽  
Endothelial Cell Proliferation ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

Prostacyclin (PGI2) is a major product of arachidonic acid metabolism in vascular endothelial cells. In addition to the role of exogenous agents, its production could be modulated by culture conditions : proliferative state, medium renewal, subcultivation... The use of endothelial cell growth factor (ECGF) associated with heparin has been shown to improve human endothelial cell proliferation. Here we report that human umbilical vein endothelial cells (HUVEC) grown in that medium produce less prostacyclin than without growth factor.HUVEC were cultured in RPMI-199 1:1 + 20% fetal calf serum, added or not with ECGF (Bovine hypothalamus extract BTI Cambridge, 24 ug/ml) and heparin (from porcine intestinal mucosa, Signa, 90 ug/ml). After 4 days in culture, medium was removed and replaced by Tyrode Hepes buffer and basal production was measured after 20 min. Cells were then submitted to 5 min thrombin to assess PGI2 production in stimulated conditions. PGI2 production was estimated by specific radioimmunoassay for 6 keto PGFjalpha. For each point, cell number in the culture was counted after Trypsin EDTA treatment. In the present study, cells grown in ECGF-heparin medium produce lower amount of PGI2, compared to heparin or control medium. This result was observed in both basal and stimulated conditions. For each medium (ECGF-heparin, heparin, control), correlations between PGI2 production per cell and log cell density were shown to be significantly negative.These observations suggest that ECGF effect on PGI2 production could be a consequence of its growth factor activity, notably by the fact that it leads to an endothelial monolayer made of more numerous cells. Since it is now suggested by a number of clinical observations that PGI2 is rather produced in pathological conditions, culture models showing a weak production of PGI2 appear in that connection doser to the physiological conditions.

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.

Aggretin, a snake venom–derived endothelial integrin α2β1 agonist, induces angiogenesis via expression of vascular endothelial growth factor

Blood ◽  
2004 ◽  
Vol 103 (6) ◽  
pp. 2105-2113 ◽  
Author(s):  
Ching-Hu Chung ◽  
Wen-Bin Wu ◽  
Tur-Fu Huang
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Umbilical Vein ◽  
Endothelial Cell Proliferation ◽  
Vascular Endothelial ◽  
Angiogenic Effect ◽  
Endothelial Growth Factor

Abstract Aggretin, a collagen-like α2β1 agonist purified from Calloselasma rhodostoma venom, was shown to increase human umbilical vein endothelial cell (HUVEC) proliferation and HUVEC migration toward immobilized aggretin was also increased. These effects were blocked by A2-IIE10, an antibody raised against integrin α2. Aggretin bound to HUVECs in a dose-dependent and saturable manner, which was specifically inhibited by A2-IIE10, as examined by flow cytometry. Aggretin elicited significant angiogenic effects in both in vivo and in vitro angiogenesis assays, and incubation of HUVECs with aggretin activated phosphatidylinositol 3-kinase (PI3K), Akt, and extracellular-regulated kinase 1/2 (ERK1/2); these effects were blocked by A2-IIE10 or vascular endothelial growth factor (VEGF) monoclonal antibody (mAb). The angiogenic effect induced by aggretin may be via the production of VEGF because the VEGF level was elevated and VEGF mAb pretreatment inhibited Akt/ERK1/2 activation as well as the in vivo angiogenesis induced by aggretin. The VEGF production induced by aggretin can be blocked by A2-IIE10 mAb pretreatment. In conclusion, aggretin induces endothelial cell proliferation, migration, and angiogenesis by interacting with integrin α2β1, leading to activation of PI3K, Akt, and ERK1/2 pathways, and the increased expression of VEGF may be responsible for its angiogenic activity.

scholarly journals Functional analysis of the cytoplasmic domain of the integrin α1 subunit in endothelial cells

Blood ◽  
2008 ◽  
Vol 112 (8) ◽  
pp. 3242-3254 ◽  
Author(s):  
Tristin D. Abair ◽  
Nada Bulus ◽  
Corina Borza ◽  
Munirathinam Sundaramoorthy ◽  
Roy Zent ◽  
...  
Keyword(s):  
Amino Acids ◽  
Cell Proliferation ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Molecular Mechanisms ◽  
Cytoplasmic Tail ◽  
Endothelial Cell Proliferation ◽  
Collagen Type Iv ◽  
Cell Functions ◽  
Α1 Subunit

Abstract Integrin α1β1, the major collagen type IV receptor, is expressed by endothelial cells and plays a role in both physiologic and pathologic angiogenesis. Because the molecular mechanisms whereby this collagen IV receptor mediates endothelial cell functions are poorly understood, truncation and point mutants of the integrin α1 subunit cytoplasmic tail (amino acids 1137-1151) were generated and expressed into α1-null endothelial cells. We show that α1-null endothelial cells expressing the α1 subunit, which lacks the entire cytoplasmic tail (mutant α1-1136) or expresses all the amino acids up to the highly conserved GFFKR motif (mutant α1-1143), have a similar phenotype to parental α1-null cells. Pro1144 and Leu1145 were shown to be necessary for α1β1-mediated endothelial cell proliferation; Lys1146 for adhesion, migration, and tubulogenesis and Lys1147 for tubulogenesis. Integrin α1β1–dependent endothelial cell proliferation is primarily mediated by ERK activation, whereas migration and tubulogenesis require both p38 MAPK and PI3K/Akt activation. Thus, distinct amino acids distal to the GFFKR motif of the α1 integrin cytoplasmic tail mediate activation of selective downstream signaling pathways and specific endothelial cell functions.

Platelet-rich Plasmas: Growth Factor Content and Roles in Wound Healing

2005 ◽  
Vol 84 (5) ◽  
pp. 434-439 ◽  
Author(s):  
J.-P. Fréchette ◽  
I. Martineau ◽  
G. Gagnon
Keyword(s):  
Wound Healing ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Umbilical Vein ◽  
Interleukin 1 ◽  
Factor Content ◽  
Umbilical Vein Endothelial Cells ◽  
Angiopoietin 2 ◽  
Mitogenic Potential

Platelet-rich plasmas (PRPs) are used in a variety of clinical applications, based on the premise that higher growth factor content should promote better healing. In this study, we have determined the effects of calcium and thrombin on the release of EGF, TGF-α, IGF-1, Ang-2 and IL-1β from PRPs, and assessed the mitogenic potential of PRP supernatants on osteoblast and endothelial cell division. ELISA assays indicate that (i) mean growth factor concentrations vary from traces (TGF-α) to 5.5 ng/mL (IGF-1), (ii) there are significant variations in growth factor concentrations between individuals, and (iii) calcium and thrombin regulate growth factor release, synthesis, and/or degradation in stereotyped patterns that are specific to each growth factor. PRP supernatants promote strong osteoblast and endothelial cell divisions, supporting the concept that PRPs may be beneficial in wound healing. Abbreviations: PRPs, platelet-rich plasmas; GFs, growth factors; EGF, epidermal growth factor; TGF-α, transforming growth factor-alpha; IGF-1, insulin-like growth factor-1; Ang-2, angiopoietin-2; IL-1β, interleukin-1 beta; HUVECs, human umbilical vein endothelial cells; hFOB 1.19, human fetal osteoblasts; and FBS, fetal bovine serum.

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.

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