The contribution of different adipose tissue depots to plasma plasminogen activator inhibitor-1 (PAI-1) levels

Blood Reviews ◽  
2016 ◽  
Vol 30 (6) ◽  
pp. 421-429 ◽  
Author(s):  
Sunelle A. Barnard ◽  
Marlien Pieters ◽  
Zelda De Lange
Keyword(s):  
Adipose Tissue ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Adipose Tissue Depots ◽  
Activator Inhibitor ◽  
Pai 1

Impairment of adipose tissue development by hypoxia is not mediated by plasminogen activator inhibitor-1

2006 ◽  
Vol 95 (01) ◽  
pp. 174-181 ◽  
Author(s):  
Fabrizio Semeraro ◽  
Gabor Voros ◽  
Désiré Collen ◽  
H. Lijnen
Keyword(s):  
Adipose Tissue ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Development ◽  
Plasminogen Activator Inhibitor 1 ◽  
Adipose Tissue Development ◽  
Activator Inhibitor ◽  
Pai 1

SummaryHypoxia in rodents and humans is associated with a reduction of body fat on the one hand, and with enhanced expression of plasminogen activator inhibitor-1 (PAI-1), the main inhibitor of the fibrinolytic system, on the other hand. It was the objective of this study to investigate whether impairment of adipose tissue development by hypoxia may be mediated by PAI-1. Five week old male wild-type (WT) C57Bl/6 mice were fed a standard (SFD) or high fat (HFD) diet and kept under normoxic or hypoxic (10% O2) conditions. In addition, PAI-1 deficient mice and WT littermates were kept on HFD under normoxia or hypoxia. In vitro, the effect of hypoxia (2% O2) was investigated on differentiation of 3T3-L1 cells into adipocytes. Hypoxia induced a significant reduction of weight gain in WT mice on either SFD or HFD, accompanied by lower weights of subcutaneous (SC) and gonadal (GON) fat. Under hypoxic conditions, adipocytes in the adipose tissues were significantly smaller, whereas blood vessel size and density were larger. Serum PAI-1 levels were enhanced in hypoxic mice on SFD but not on HFD, and overall did not correlate with the observed changes in adipose tissue composition. Furthermore, the effects of hypoxia on adipose tissue in mice on HFD were not affected by deficiency of PAI-1. The inhibiting effect of hypoxia on in vitro preadipocyte differentiation was not mediated by PAI-1 activity. In conclusion, impairment of in vivo adipose tissue development and in vitro differentiation of preadipocytes by hypoxia is not mediated by PAI-1.

scholarly journals The Role of Plasminogen Activator Inhibitor-1 in the Metabolic Syndrome and Its Regulation

2014 ◽  
Vol 3 (6) ◽  
pp. 36 ◽  
Author(s):  
Martha Phelan ◽  
David M. Kerins
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
The Metabolic Syndrome ◽  
Activator Inhibitor ◽  
Pai 1

<p>Obesity is a major risk factor for cardiovascular disease (CVD). Lipid abnormalities, hypertension, impaired glucose tolerance or diabetes, are cardiovascular risk factors that are frequently present in patients with obesity. Haemostatic and fibrinolytic disturbances are also considered to be important risk factors for CVD hence, a potential link between CVD, obesity and the metabolic syndrome arises. Regulation of the fibrinolytic system can occur at the level of plasminogen activators and plasminogen activator inhibitor-1 (PAI-1). PAI-1, a glycoprotein, is one of the most important inhibitors of fibrinolysis. Regulation of this serine protease inhibitor may have a beneficial effect on other conditions associated with the metabolic syndrome. Human adipose tissue is a source of PAI-1. PAI-1 production may in turn be controlled by a number of hormones and cytokines which are secreted by adipose tissue in addition to dietary factors. In this review we summarise the current knowledge regarding the role of altered fibrinolytic function in obesity, CVD and hence the metabolic syndrome. Regulatory factors including different dietary components, weight loss and dietary intervention will also be discussed.</p>

Effect of plasminogen activator inhibitor-1 deficiency on nutritionally-induced obesity in mice

2005 ◽  
Vol 93 (05) ◽  
pp. 816-819 ◽  
Author(s):  
Roger Lijnen
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Plasminogen Activator ◽  
High Fat Diet ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
High Fat ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor ◽  
Pai 1

SummaryPlasminogen activator inhibitor-1 (PAI-1) is the main physiological inhibitor of tissue-type (t-PA) and urokinase-type (u-PA) plasminogen activator. Recent studies in murine models have yielded apparently conflicting data on a potential role of PAI-1 in adipose tissue development and obesity. To reinvestigate this issue, we have rederived PAI-1 deficient (PAI-1-/-) and wild-type (WT) mice and generated true littermates in a 81.25% C57Bl/6: 18.75% 129 SV genetic background. Male 5-week-old PAI-1-/- and WT mice were kept on a high fat diet (20.1 kJ/g) for 15 weeks. Body weight gain was comparable for both genotypes, and at the time of sacrifice total body weights (39 ± 1.1 versus 41 ± 1.2 g) as well as the weights of subcutaneous (SC, 1,520 ± 110 versus 1,480 ± 110 mg) adipose tissue were not significantly different. In contrast, the gonadal (GON, 1,900 ± 43 versus 1,510 ± 86 mg, p < 0.005) tissue mass was larger in PAI-1-/- mice. Plasma levels of insulin, leptin, glucose, triglycerides, total, HDL and LDL cholesterol were comparable for both genotypes. Immunohisto-chemical analysis of SC and GON adipose tissues did not reveal differences in adipocyte size or number between both genotypes, whereas blood vessel density was also comparable for GON fat but lower in SC fat of WT mice. Thus, this study in littermate mice on high fat diet did not reveal an effect of PAI-1 deficiency on body weight, and a differential effect on SC and GON adipose tissue.

scholarly journals Plasminogen activator inhibitor-1 and haemostasis in obesity

2001 ◽  
Vol 60 (3) ◽  
pp. 341-347 ◽  
Author(s):  
Nicola J. Mutch ◽  
Heather M. Wilson ◽  
Nuala A. Booth
Keyword(s):  
Adipose Tissue ◽  
Plasminogen Activator ◽  
Transforming Growth Factor ◽  
Plasminogen Activator Inhibitor ◽  
Cell Types ◽  
Plasminogen Activator Inhibitor 1 ◽  
Increased Risk ◽  
Human Material ◽  
Activator Inhibitor ◽  
Pai 1

The connection between obesity and disordered haemostasis is well established, but incompletely understood. There is a strong link between inhibition of fibrinolysis and obesity, and elevation of the plasma inhibitor, plasminogen activator inhibitor-1 (PAI-1), is regarded as a central factor. Here we explore the increased risk of atherothrombotic disorders in obese subjects, and the evidence for metabolic and genetic causes. There is a clear relationship between plasma PAI-1 and obesity, and adipose tissue synthesises PAI-1, as has been shown in mouse and rat models, and more recently in human material. This tissue also produces several effector molecules that can up regulate PAI-1. These molecules include transforming growth factor b, tumour necrosis factor a, angiotensin II and interleukin 6, all of which up regulate PAI-1 in various cell types. The issue of whether adipose tissue directly contributes to plasma PAI-1, or whether it primarily contributes indirectly, its products stimulating other cells to produce PAI-1 that feeds into the plasma pool, is not yet resolved. Finally, we briefly examine other proteins of haemostasis that are products of adipose tissue. Further studies are needed to define the regulation of these proteins, in adipose tissue itself and in other cells influenced by its products, in order to extend recent insights into the links between obesity and haemostasis.

scholarly journals Plasminogen Activator Inhibitor-1 is Regulated Through Dietary Fat Intake and Heritability: Studies in Twins

2017 ◽  
Vol 20 (4) ◽  
pp. 338-348 ◽  
Author(s):  
Anna Janina Engstler ◽  
Turid Frahnow ◽  
Michael Kruse ◽  
Andreas Friedrich Hermann Pfeiffer ◽  
Ina Bergheim
Keyword(s):  
Adipose Tissue ◽  
Mrna Expression ◽  
Plasminogen Activator ◽  
Plasma Concentrations ◽  
Plasminogen Activator Inhibitor ◽  
Fatty Tissue ◽  
Plasminogen Activator Inhibitor 1 ◽  
The Impact ◽  
Activator Inhibitor ◽  
Pai 1

In different pathophysiological conditions plasminogen activator inhibitor-1 (PAI-1) plasma concentrations are elevated. As dietary patterns are considered to influence PAI-1 concentration, we aimed to determine active PAI-1 plasma concentrations and mRNA expression in adipose tissue before and after consumption of a high-fat diet (HFD) and the impact of additive genetic effects herein in humans. For 6 weeks, 46 healthy, non-obese pairs of twins (aged 18–70) received a normal nutritionally balanced diet (ND) followed by an isocaloric HFD for 6 weeks. Active PAI-1 plasma levels and PAI-1 mRNA expression in subcutaneous adipose tissue were assessed after the ND and after 1 and 6 weeks of HFD. Active PAI-1 plasma concentrations and PAI-1 mRNA expression in adipose tissue were significantly increased after both 1 and 6 weeks of HFD when compared to concentrations determined after ND (p< .05), with increases of active PAI-1 being independent of gender, age, or changes of BMI and intrahepatic fat content, respectively. However, analysis of covariance suggests that serum insulin concentration significantly affected the increase of active PAI-1 plasma concentrations. Furthermore, the increase of active PAI-1 plasma concentrations after 6 weeks of HFD was highly heritable (47%). In contrast, changes in PAI-1 mRNA expression in fatty tissue in response to HFD showed no heritability and were independent of all tested covariates. In summary, our data suggest that even an isocaloric exchange of macronutrients — for example, a switch to a fat-rich diet — affects PAI-1 concentrations in humans and that this is highly heritable.

TNF-α, but not IL-6, stimulates plasminogen activator inhibitor-1 expression in human subcutaneous adipose tissue

2005 ◽  
Vol 98 (6) ◽  
pp. 2019-2023 ◽  
Author(s):  
Peter Plomgaard ◽  
Pernille Keller ◽  
Charlotte Keller ◽  
Bente Klarlund Pedersen
Keyword(s):  
Adipose Tissue ◽  
Mrna Expression ◽  
Plasminogen Activator ◽  
Subcutaneous Adipose Tissue ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Tnf Α ◽  
Subcutaneous Adipose ◽  
Activator Inhibitor ◽  
Pai 1

Plasminogen activator inhibitor-1 (PAI-1) is produced by adipose tissue, and elevated PAI-1 levels in plasma are a risk factor in the metabolic syndrome. We investigated the regulatory effects of TNF-α and IL-6 on PAI-1 gene induction in human adipose tissue. Twenty healthy men underwent a 3-h infusion of either recombinant human TNF-α ( n = 8), recombinant human IL-6 ( n = 6), or vehicle ( n = 6). Biopsies were obtained from the subcutaneous abdominal adipose tissue at preinfusion, at 1, 2, and 3 h during the infusion, and at 2 h after the infusion. The mRNA expression of PAI-1 in the adipose tissue was measured using real-time PCR. The plasma levels of TNF-α and IL-6 reached 18 and 99 pg/ml, respectively, during the infusions. During the TNF-α infusion, adipose PAI-1 mRNA expression increased 2.5-fold at 1 h, 6-fold at 2 h, 9-fold at 3 h, and declined to 2-fold 2 h after the infusion stopped but did not change during IL-6 infusion and vehicle. These data demonstrate that TNF-α rather than IL-6 stimulates an increase in PAI-1 mRNA in the subcutaneous adipose tissue, suggesting that TNF-α may be involved in the pathogenesis of related metabolic disorders.

943: Plasminogen Activator Inhibitor 1 (PAI-1) is Increased in Human Peyronie's Disease

2005 ◽  
Vol 173 (4S) ◽  
pp. 255-255 ◽  
Author(s):  
Hugo H. Davila ◽  
Thomas R. Magee ◽  
Freddy Zuniga ◽  
Jacob Rajfer ◽  
Nestor F. GonzalezCadavid
Keyword(s):  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Peyronie’S Disease ◽  
Plasminogen Activator Inhibitor 1 ◽  
Peyronie's Disease ◽  
Activator Inhibitor ◽  
Pai 1

Relationship of Plasminogen Activator Inhibitor-1 Levels following Thrombolytic Therapy with rt-PA as Compared to Streptokinase and Patency of Infarct Related Coronary Artery

1999 ◽  
Vol 82 (07) ◽  
pp. 104-108 ◽  
Author(s):  
Franck Paganelli ◽  
Marie Christine Alessi ◽  
Pierre Morange ◽  
Jean Michel Maixent ◽  
Samuel Lévy ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Thrombolytic Therapy ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Control Group ◽  
Plasminogen Activator Inhibitor 1 ◽  
Vessel Patency ◽  
Activator Inhibitor ◽  
Pai 1

Summary Background: Type 1 plasminogen activator inhibitor (PAI-1) is considered to be risk factor for acute myocardial infarction (AMI). A rebound of circulating PAI-1 has been reported after rt-PA administration. We investigated the relationships between PAI-1 levels before and after thrombolytic therapy with streptokinase (SK) as compared to rt-PA and the patency of infarct-related arteries. Methods and Results: Fifty five consecutive patients with acute MI were randomized to strep-tokinase or rt-PA. The plasma PAI-1 levels were studied before and serially within 24 h after thrombolytic administration. Vessel patency was assessed by an angiogram at 5 ± 1days. The PAI-1 levels increased significantly with both rt-PA and SK as shown by the levels obtained from a control group of 10 patients treated with coronary angioplasty alone. However, the area under the PAI-1 curve was significantly higher with SK than with rt-PA (p <0.01) and the plasma PAI-1 levels peaked later with SK than with rt-PA (18 h versus 3 h respectively). Conversely to PAI-1 levels on admission, the PAI-1 levels after thrombolysis were related to vessel patency. Plasma PAI-1 levels 6 and 18 h after SK therapy and the area under the PAI-1 curve were significantly higher in patients with occluded arteries (p <0.002, p <0.04 and p <0.05 respectively).The same tendency was observed in the t-PA group without reaching significance. Conclusions: This study showed that the PAI-1 level increase is more pronounced after SK treatment than after t-PA treatment. There is a relationship between increased PAI-1 levels after thrombolytic therapy and poor patency. Therapeutic approaches aimed at quenching PAI-1 activity after thrombolysis might be of interest to improve the efficacy of thrombolytic therapy for acute myocardial infarction.

Fibrinolysis in Normal Subjects - Comparison Between Plasminogen Activator Inhibitor and Other Components of the Fibrinolytic System

1988 ◽  
Vol 59 (02) ◽  
pp. 299-303 ◽  
Author(s):  
Grazia Nicoloso ◽  
Jacques Hauert ◽  
Egbert K O Kruithof ◽  
Guy Van Melle ◽  
Fedor Bachmann
Keyword(s):  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Plasminogen Activator Inhibitor ◽  
Venous Occlusion ◽  
Venous Stasis ◽  
Plasminogen Activator Inhibitor 1 ◽  
Plate Assay ◽  
Fibrin Plate ◽  
Activator Inhibitor ◽  
Pai 1

SummaryWe analyzed fibrinolytic parameters in 20 healthy men and 20 healthy women, aged from 25 to 59, before and after 10 and 20 min venous occlusion. The 10 min post-occlusion fibrinolytic activity measured directly in diluted unfractionated plasma by a highly sensitive 125I-fibrin plate assay correlated well with the activity of euglobulins determined by the classical fibrin plate assay (r = 0.729), but pre-stasis activities determined with these two methods did not correlate (r = 0.084). The enhancement of fibrinolytic activity after venous occlusion was mainly due to an increase of t-PA in the occluded vessels (4-fold increase t-PA antigen after 10 min and 8-fold after 20 min venous occlusion). Plasminogen activator inhibitor (PAI) activity and plasminogen activator inhibitor 1 (PAI-1)1 antigen levels at rest showed considerable dispersion ranging from 1.9 to 12.4 U/ml, respectively 6.9 to 77 ng/ml. A significant increase of PAI-1 antigen levels was observed after 10 and 20 min venous occlusion. At rest no correlation was found between PAI activity or PAI-1 antigen levels and the fibrinolytic activity measured by 125I-FPA. However, a high level of PAI-1 at rest was associated with a high prestasis antigen level of t-PA and a low fibrinolytic response after 10 min of venous stasis. Since the fibrinolytic response inversely correlated with PAI activity at rest, we conclude that its degree depends mainly on the presence of free PAI.

Sign in / Sign up

Export Citation Format

Share Document