Relationships between Fibrinolytic and Inflammatory Parameters in Human Adipose Tissue: Strong Contribution of TNFα Receptors to PAI-1 Levels

Bastelica, Delphine; Mavri, Alenka; Verdier, Monique; Berthet, B.; Juhan‐Vague, I.; Alessi, Marie‐Christine

doi:10.1055/s-0037-1613241

Cited by 37 publications

(27 citation statements)

References 37 publications

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“…57,58 Moreover, the invalidation of both TNF receptors decreased TGF-beta expression in the adipose tissue, 57 and in humans, TNF receptors, TGF-beta, and PAI-1 levels were strongly correlated within adipose tissue. 59,60 These results suggest that the TNF and TGF-beta pathways are connected within adipose tissue and may both control PAI-1 expression. The possible connection between insulin resistance, TGF-beta, and PAI-1 is further supported by the lowered expression of PAI-1 in FOXC2 ϩ/Ϫ mice in response to TGF-beta1 treatment 61 because FOXC2 has been implicated in insulin resistance.…”

Section: Arguments For the Contribution Of Tnf And Tgf-beta To Pai-1 mentioning

confidence: 81%

PAI-1 and the Metabolic Syndrome

Alessi

Juhan‐Vague

2006

ATVB

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332

126

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Abstract-The link between plasminogen activator inhibitor (PAI)-1 and the metabolic syndrome with obesity was established many years ago. Increased PAI-1 level can be now considered a true component of the syndrome. The metabolic syndrome is associated with an increased risk of developing cardiovascular disease, and PAI-1 overexpression may participate in this process. The mechanisms of PAI-1 overexpression during obesity are complex, and it is conceivable that several inducers are involved at the same time at several sites of synthesis. Interestingly, recent in vitro and in vivo studies showed that besides its role in atherothrombosis, PAI-1 is also implicated in adipose tissue development and in the control of insulin signaling in adipocytes. These findings suggest PAI-1 inhibitors serve in the control of atherothrombosis and insulin resistance.

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Section: Arguments For the Contribution Of Tnf And Tgf-beta To Pai-1 mentioning

confidence: 81%

PAI-1 and the Metabolic Syndrome

Alessi

Juhan‐Vague

2006

ATVB

Self Cite

332

126

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“…In addition, the stromal cell fraction contained more PAI-1 mRNA than the adipocyte fraction. 32 However, in a study by Birgel et al 33 using an established in vitro model of human stromal cells undergoing in vitro adipose differentiation, it was demonstrated that there is a two-fold increase in the production of PAI-1 during the course of adipose differentiation at least under these experimental conditions. Again, the reason for this inconsistency is unclear.…”

Section: 24mentioning

confidence: 94%

Obesity and impaired fibrinolysis: role of adipose production of plasminogen activator inhibitor-1

2004

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Obesity is the central promoter of the metabolic syndrome which also includes disturbed fibrinolysis in addition to hypertension, dyslipidaemia and impaired glucose tolerance/type 2 diabetes mellitus. Plasminogen activator inhibitor-1 (PAI-1) is the most important endogenous inhibitor of tissue plasminogen activator and uro-plasminogen activator, and is a main determinant of fibrinolytic activity. There is now compelling evidence that obesity and, in particular, an abdominal type of body fat distribution are associated with elevated PAI-1 antigen and activity levels. Recent studies established that PAI-1 is expressed in adipose tissue. The greater the fat cell size and the adipose tissue mass, the greater is the contribution of adipose production to circulating PAI-1. Experimental data show that visceral adipose tissue has a higher capacity to produce PAI-1 than subcutaneous adipose tissue. Studies in human adipocytes indicate that PAI-1 synthesis is upregulated by insulin, glucocorticoids, angiotensin II, some fatty acids and, most potently, by cytokines such as tumour necrosis factor-a and transforming growth factor-b, whereas catecholamines reduce PAI-1 production. Interestingly, pharmacological agents such as thiazolidinediones, metformin and AT 1 -receptor antagonists were found to reduce adipose expression of PAI-1. In addition, weight loss by dietary restriction or comprehensive lifestyle modification is effective in lowering PAI-1 plasma levels. In conclusion, impaired fibrinolysis in obesity is probably also due to an increased expression of PAI-1 in adipose tissue. An altered function of the endocrine system and an impaired auto-/paracrine function at the fat cell levels may mediate this disturbance of the fibrinolytic system and thereby increase the risk for cardiovascular disease.

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“…PAI-1 can be produced in hepatocytes, 13 endothelial cells 18 and adipocytes. 10 Hepatic PAI-1 overproduction can cause systemic fibrinolytic system shutdown as shown by consequences of induction of the MET oncogene in mouse liver resulting in increased hepatic PAI-1 production and disseminated intravascular coagulation. 19 Binding of HGF to its specific receptor c-Met induces activation of intracellular tyrosine kinase domain of the c-Met and recruits a number of intracellular signaling molecules.…”

Section: Imagawa Et Almentioning

confidence: 99%

“…9 Adipose tissue may be an important source of PAI-1 with excess fat and subclinical inflammation. 10 However, fatty liver is common in metabolic syndrome, 11 and liver steatosis is strongly related to plasma PAI-1 levels, 12 suggesting that liver is an important source of increased circulating PAI-1. This study was designed to characterize molecular mechanisms influencing altered hepatic PAI-1 expression by HGF and to identify potential therapeutic approaches for attenuation of HGF-induced PAI-1 expression.…”

mentioning

confidence: 99%

Hepatocyte Growth Factor Regulates E Box–Dependent Plasminogen Activator Inhibitor Type 1 Gene Expression in HepG2 Liver Cells

Imagawa

Fujii

Dong

et al. 2006

ATVB

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Objective-We sought to determine the etiologic mechanism of pleiotropic growth factor, hepatocyte growth factor (HGF), as a regulator of hepatic synthesis of plasminogen activator inhibitor (PAI)-1, the physiological inhibitor of fibrinolysis and a potential inducer of atherothrombosis. Methods and Results-HGF increased PAI-1 mRNA expression and PAI-1 protein accumulation in the conditioned media of human liver-derived HepG2 cells, and increased hepatic PAI-1 mRNA expression in vivo in mice. HGF-inducible PAI-1 mRNA was attenuated by U0126, a specific inhibitor of mitogen-activated protein kinase (MAPK) kinase, and genistein, an inhibitor of tyrosine kinase. HGF increased the human PAI-1 promoter (Ϫ829 to ϩ36 bp) activity, and deletion and mutation analysis uncovered a functional E box (5Ј-CACATG-3Ј) at positions Ϫ158 to Ϫ153 bp. Electrophoretic mobility shift assays demonstrated that this E box binds upstream stimulatory factors (USFs). HGF phosphorylated USFs through MAPK and tyrosine kinase pathways. Co-transfection of USF1 expression vector increased PAI-1 promoter activity. Sterol regulatory element-binding protein-1 attenuated HGF-inducible PAI-1 promoter activity. Conclusions-Because

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Relationships between Fibrinolytic and Inflammatory Parameters in Human Adipose Tissue: Strong Contribution of TNFα Receptors to PAI-1 Levels

Cited by 37 publications

References 37 publications

PAI-1 and the Metabolic Syndrome

PAI-1 and the Metabolic Syndrome

Obesity and impaired fibrinolysis: role of adipose production of plasminogen activator inhibitor-1

Hepatocyte Growth Factor Regulates E Box–Dependent Plasminogen Activator Inhibitor Type 1 Gene Expression in HepG2 Liver Cells

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