scholarly journals Microarray-based Analysis of Anti-angiogenic Activity of Demethoxycurcumin on Human Umbilical Vein Endothelial Cells: Crucial Involvement of the Down-regulation of Matrix Metalloproteinase

2002 ◽  
Vol 93 (12) ◽  
pp. 1378-1385 ◽  
Author(s):  
Jin Hee Kim ◽  
Joong Sup Shim ◽  
Seok-Ki Lee ◽  
Kyu-Won Kim ◽  
Sun Young Rha ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Matrix Metalloproteinase ◽  
Umbilical Vein ◽  
Down Regulation ◽  
Angiogenic Activity ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

scholarly journals Suppression of Angiogenesis by Targeting Cyclin-Dependent Kinase 7 in Human Umbilical Vein Endothelial Cells and Renal Cell Carcinoma: An In Vitro and In Vivo Study

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1469 ◽  
Author(s):  
Chung-Sheng Shi ◽  
Kuan-Lin Kuo ◽  
Mei-Sin Chen ◽  
Po-Ming Chow ◽  
Shing-Hwa Liu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Endothelial Cells ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Antitumor Effects ◽  
Angiogenic Activity ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

Cancer cells rely on aberrant transcription for growth and survival. Cyclin-dependent kinases (CDKs) play critical roles in regulating gene transcription by modulating the activity of RNA polymerase II (RNAPII). THZ1, a selective covalent inhibitor of CDK7, has antitumor effects in several human cancers. In this study, we investigated the role and therapeutic potential of CDK7 in regulating the angiogenic activity of endothelial cells and human renal cell carcinoma (RCC). Our results revealed that vascular endothelial growth factor (VEGF), a critical activator of angiogenesis, upregulated the expression of CDK7 and RNAPII, and the phosphorylation of RNAPII at serine 5 and 7 in human umbilical vein endothelial cells (HUVECs), indicating the transcriptional activity of CDK7 may be involved in VEGF-activated angiogenic activity of endothelium. Furthermore, through suppressing CDK7 activity, THZ1 suppressed VEGF-activated proliferation and migration, as well as enhanced apoptosis of HUVECs. Moreover, THZ1 inhibited VEGF-activated capillary tube formation and CDK7 knockdown consistently diminished tube formation in HUVECs. Additionally, THZ1 reduced VEGF expression in human RCC cells (786-O and Caki-2), and THZ1 treatment inhibited tumor growth, vascularity, and angiogenic marker (CD31) expression in RCC xenografts. Our results demonstrated that CDK7-mediated transcription was involved in the angiogenic activity of endothelium and human RCC. THZ1 suppressed VEGF-mediated VEGFR2 downstream activation of angiogenesis, providing a new perspective for antitumor therapy in RCC patients.

Lysophosphatidylcholine Decreases the Synthesis of Tissue Factor Pathway Inhibitor in Human Umbilical Vein Endothelial Cells

1998 ◽  
Vol 79 (01) ◽  
pp. 217-221 ◽  
Author(s):  
Koichi Kokame ◽  
Toshiyuki Miyata ◽  
Naoaki Sato ◽  
Hisao Kato
Keyword(s):  
Endothelial Cells ◽  
Mrna Expression ◽  
Tissue Factor ◽  
Tissue Factor Pathway Inhibitor ◽  
Umbilical Vein ◽  
Mrna Levels ◽  
Down Regulation ◽  
Human Umbilical Vein ◽  
Tissue Factor Pathway ◽  
Umbilical Vein Endothelial Cells

SummaryThrombotic complications are frequently associated with atherosclerosis. Lysophosphatidylcholine (LPC), a component accumulated in oxidatively modified LDL (ox-LDL), is known to play a crucial role in the initiation and progression of atherosclerotic vascular lesions. Since a vascular anticoagulant, tissue factor pathway inhibitor (TFPI), has the function of regulating the initial reaction of tissue factor (TF)-induced coagulation, we investigated the effect of LPC on TFPI synthesis in cultured human umbilical vein endothelial cells (HUVEC). The treatment of HUVEC with LPC for 24 h decreased TFPI antigen levels in both the culture medium and the cell lysate in a dose-dependent manner. Northern blot analysis revealed that LPC caused a time-dependent decrease in the TFPI mRNA levels. The levels of TFPI antigen and mRNA were decreased to 72% and 38%, respectively, by the incubation with 50 μM LPC for 24 h. The down-regulation by LPC of TFPI mRNA expression was not observed in the presence of cycloheximide, suggesting that protein synthesis was involved in the suppression of TFPI mRNA expression. The TFPI mRNA levels in actinomycin D-treated cells were relatively stable, indicating that the down-regulation of TFPI mRNA by LPC would be partly explained by the enhanced mRNA destabilization. In contrast to the significant down-regulatory effects of LPC on TFPI expression, LPC did not induce TF mRNA expression in HUVEC. These results indicate that LPC accumulated in the atherosclerotic vascular wall would suppress endothelial TFPI synthesis, reducing the antithrombotic property of endothelial cells.

scholarly journals Study of pro-angiogenic activity of astilbin on human umbilical vein endothelial cells in vitro and zebrafish in vivo

RSC Advances ◽  
2019 ◽  
Vol 9 (40) ◽  
pp. 22921-22930 ◽  
Author(s):  
Kongpeng Lv ◽  
Qin Ren ◽  
Xingyan Zhang ◽  
Keda Zhang ◽  
Jia Fei ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Angiogenic Activity ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

Pro-angiogenic activity of astilbin on endothelial cells in vitro and zebrafish in vivo.

Estrogen Promotes Angiogenic Activity in Human Umbilical Vein Endothelial Cells In Vitro and in a Murine Model

Circulation ◽  
1995 ◽  
Vol 91 (3) ◽  
pp. 755-763 ◽  
Author(s):  
David E. Morales ◽  
Kelly A. McGowan ◽  
Derrick S. Grant ◽  
Shailendra Maheshwari ◽  
Deepa Bhartiya ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Murine Model ◽  
Umbilical Vein ◽  
Angiogenic Activity ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

Activation of pro-(matrix metalloproteinase-2) (pro-MMP-2) by thrombin is membrane-type-MMP-dependent in human umbilical vein endothelial cells and generates a distinct 63 kDa active species

2001 ◽  
Vol 357 (1) ◽  
pp. 107-115 ◽  
Author(s):  
Marc A. LAFLEUR ◽  
Morley D. HOLLENBERG ◽  
Susan J. ATKINSON ◽  
Vera KNÄUPER ◽  
Gillian MURPHY ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Matrix Metalloproteinase ◽  
Umbilical Vein ◽  
Coagulation Cascade ◽  
Matrix Metalloproteinase 2 ◽  
Intermediate Form ◽  
Dependent Manner ◽  
Human Umbilical Vein ◽  
Membrane Type ◽  
Umbilical Vein Endothelial Cells

Thrombin, a critical enzyme in the coagulation cascade, has also been associated with angiogenesis and activation of the zymogen form of matrix metalloproteinase-2 (MMP-2 or gelatinase-A). We show that thrombin activated pro-MMP-2 in a dose- and time-dependent manner in cultured human umbilical-vein endothelial cells (HUVECs) to generate a catalytically active 63kDa protein that accumulated as the predominant form in the conditioned medium. This 63kDa thrombin-activated MMP-2 is distinct from the 62kDa species found following concanavalin A or PMA stimulated pro-MMP-2 activation. Hirudin and leupeptin blocked thrombin-induced pro-MMP-2 activation, demonstrating that the proteolytic activity of thrombin is essential. However, activation was also dependent upon membrane-type-MMP (MT-MMP) action, since it was blocked by EDTA, o-phenanthroline, hydroxamate metalloproteinase inhibitors, tissue inhibitor of metalloproteinase-2 (TIMP-2) and TIMP-4, but not TIMP-1. Thrombin inefficiently cleaved recombinant 72kDa pro-MMP-2, but efficiently cleaved the 64kDa MT-MMP-processed intermediate form in the presence of cells. Thrombin also rapidly (within 1h) increased cellular MT-MMP activity, and at longer time points (>6h) it increased expression of MT1-MMP mRNA and protein. Thus signalling via proteinase-activated receptors (PARs) may play a role in thrombin-induced MMP-2 activation, though this does not appear to involve PAR1, PAR2, or PAR4 in HUVECs. These results indicate that in HUVECs the activation of pro-MMP-2 by thrombin involves increased MT-MMP activity and preferential cleavage of the MT-MMP-processed 64kDa MMP-2 form in the presence of cells. The integration of these proteinase systems in the vascular endothelium may be important during thrombogenesis and tissue remodelling associated with neovascularization.

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