scholarly journals 2-Amino-phenoxazine-3-one Attenuates Glucose-Induced Augmentation of Embryonic Form of Myosin Heavy Chain, Endothelin-1 and Plasminogen Activator Inhibitor-1 in Human Umbilical Vein Endothelial Cells

2005 ◽  
Vol 28 (5) ◽  
pp. 797-801 ◽  
Author(s):  
Gen Fukuda ◽  
Noriko Yoshitake ◽  
Zia Ali Khan ◽  
Masao Kanazawa ◽  
Yoko Notoya ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Myosin Heavy Chain ◽  
Plasminogen Activator ◽  
Heavy Chain ◽  
Umbilical Vein ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells ◽  
Activator Inhibitor

scholarly journals Positions of Hydroxyl Groups in Chrysin are Critical for Inhibiting Plasminogen Activator Inhibitor-1 Release from Human Umbilical Vein Endothelial Cells

2017 ◽  
Vol 12 (4) ◽  
pp. 1934578X1701200
Author(s):  
Naoki Ohkura ◽  
Kumiko Ando ◽  
Yuko Takata ◽  
Shiho Kanai ◽  
Kenichi Ishibashi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Plasminogen Activator ◽  
Umbilical Vein ◽  
Plasminogen Activator Inhibitor ◽  
Hydroxyl Groups ◽  
Plasminogen Activator Inhibitor 1 ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells ◽  
Activator Inhibitor ◽  
Pai 1

Chrysin suppresses the TNFa-induced increase in the secretion of plasma plasminogen activator inhibitor 1 (PAI-1), a risk factor for thrombotic diseases, from human umbilical vein endothelial cells (HUVECs). The present study aimed to determine the association between the location of the hydroxyl groups in chrysin to levels of PAI-1 in the medium of HUVEC stimulated with TNFα, We cultured HUVEC for 3 h in medium containing chrysin or various flavonoids and then stimulated them with TNFα (10 ng/mL) for 12 h. Levels of PAI-1 antigen measured using ELISA showed that chrysin significantly inhibited the PAI-1 increase with an IC50 of 15.6 μM. The flavones, galangin, baicalein, 5-hydroxyflavone, 6-hydroxyflavone, 7-hydroxyflavone and quercetin did not significantly inhibit the PAI-1 increase. Apigenin and luteolin were cytotoxic and thus their ability to inhibit PAI-1 production could not be evaluated. Chrysin also inhibited PAI-1 mRNA expression whereas the other compounds did not. Hydroxyl groups located in the A-5 and A-7 positions were essential for the inhibitory activity, which along with cytotoxicity, was significantly influenced by adding a third hydroxyl group.

scholarly journals Endothelial METTL3 (Methyltransferase-Like 3) Inhibits Fibrinolysis by Promoting PAI-1 (Plasminogen Activator Inhibitor-1) Expression Through Enhancing Jun Proto-Oncogene N6-Methyladenosine Modification

2021 ◽  
Author(s):  
Qin Bai ◽  
Yao Lu ◽  
Yanhua Chen ◽  
Han Zhang ◽  
Weiwei Zhang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Real Time ◽  
Plasminogen Activator ◽  
Crucial Role ◽  
Umbilical Vein ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Umbilical Vein Endothelial Cells ◽  
Activator Inhibitor ◽  
Pai 1

Objective: METTL3 (methyltransferase-like protein 3)-mediated N 6 -methyladenosine modification is the most abundant RNA modification on eukaryote mRNAs and plays a crucial role in diverse physiological and pathological processes. However, whether N 6 -methyladenosine modification has function in thrombosis is unknown. This study aims to determine the role of METTL3 in the endothelial cells-mediated thrombosis. Approach and Results: RNA-sequencing and real-time quantitative PCR revealed that the expression of PAI-1 (plasminogen activator inhibitor-1) was downregulated in METTL3 knockdown human umbilical vein endothelial cells. In vitro experiments showed that METTL3 suppressed fibrinolysis. Mechanically, RNA methylation sequencing and meRIP-quantitative real-time PCR showed that METTL3 catalyzed N 6 -methyladenosine modification on 3′ UTR of JUN mRNA. Western blotting analysis showed that METTL3 promoted JUN protein expression. Chromatin immunoprecipitation analysis demonstrated that JUN bound to the PAI-1 promoter in human umbilical vein endothelial cells. Furthermore, mice challenged with lipopolysaccharide resulted in higher METTL3 expression in vessels. Endothelial-specific knockdown of Mettl3 decreased expression of active PAI-1 in plasma and attenuated fibrin deposition in livers and lungs during endotoxemia. Conclusions: Our study reveals that METTL3-mediated N 6 -methyladenosine modification plays a crucial role in fibrinolysis and is an underlying target for the therapy of thrombotic disorders.

scholarly journals Thrombin regulation of mRNA levels of tissue plasminogen activator and plasminogen activator inhibitor-1 in cultured human umbilical vein endothelial cells

Blood ◽  
1989 ◽  
Vol 74 (1) ◽  
pp. 222-228 ◽  
Author(s):  
D Dichek ◽  
T Quertermous
Keyword(s):  
Endothelial Cells ◽  
Plasminogen Activator ◽  
Umbilical Vein ◽  
Plasminogen Activator Inhibitor ◽  
Mrna Levels ◽  
Human Umbilical Vein ◽  
Tissue Plasminogen ◽  
Umbilical Vein Endothelial Cells ◽  
Activator Inhibitor ◽  
Pai 1

Abstract Cultured human umbilical vein endothelial cells release tissue plasminogen activator (t-PA) and type 1 plasminogen activator inhibitor (PAI-1) in response to alpha thrombin stimulation. In order to study the mechanisms of thrombin stimulation, we measured changes in levels of mRNA for t-PA and PAI-1 following exposure of endothelial cells to 3 U/mL alpha thrombin. Alpha thrombin causes a significant and time- dependent increase in the mRNA levels of both t-PA and PAI-1. Catalytically inactivated diisofluorophosphate (DIP) treated thrombin and alpha thrombin pretreated with hirudin do not alter t-PA and PAI-1 mRNA levels. We conclude that the increased secretion of t-PA and PAI-1 by human umbilical vein endothelial cells in response to alpha thrombin is mediated at least partially through an increase in mRNA levels. In addition, an active thrombin catalytic site is required for these increases in mRNA to occur.

scholarly journals Thrombin regulation of mRNA levels of tissue plasminogen activator and plasminogen activator inhibitor-1 in cultured human umbilical vein endothelial cells

Blood ◽  
1989 ◽  
Vol 74 (1) ◽  
pp. 222-228 ◽  
Author(s):  
D Dichek ◽  
T Quertermous
Keyword(s):  
Endothelial Cells ◽  
Plasminogen Activator ◽  
Umbilical Vein ◽  
Plasminogen Activator Inhibitor ◽  
Mrna Levels ◽  
Human Umbilical Vein ◽  
Tissue Plasminogen ◽  
Umbilical Vein Endothelial Cells ◽  
Activator Inhibitor ◽  
Pai 1

Cultured human umbilical vein endothelial cells release tissue plasminogen activator (t-PA) and type 1 plasminogen activator inhibitor (PAI-1) in response to alpha thrombin stimulation. In order to study the mechanisms of thrombin stimulation, we measured changes in levels of mRNA for t-PA and PAI-1 following exposure of endothelial cells to 3 U/mL alpha thrombin. Alpha thrombin causes a significant and time- dependent increase in the mRNA levels of both t-PA and PAI-1. Catalytically inactivated diisofluorophosphate (DIP) treated thrombin and alpha thrombin pretreated with hirudin do not alter t-PA and PAI-1 mRNA levels. We conclude that the increased secretion of t-PA and PAI-1 by human umbilical vein endothelial cells in response to alpha thrombin is mediated at least partially through an increase in mRNA levels. In addition, an active thrombin catalytic site is required for these increases in mRNA to occur.

Sign in / Sign up

Export Citation Format

Share Document