Clustering of Thrombotic Factors with Insulin Resistance in South Asian Patients with Ischaemic Stroke

2002 ◽  
Vol 88 (12) ◽  
pp. 950-953 ◽  
Author(s):  
Andrew Catto ◽  
Peter Grant ◽  
Kirti Kain
Keyword(s):  
Insulin Resistance ◽  
Ischaemic Stroke ◽  
Plasminogen Activator ◽  
South Asian ◽  
Plasminogen Activator Inhibitor ◽  
Factor Vii ◽  
Model Assessment ◽  
Plasminogen Activator Inhibitor 1 ◽  
Asian Patients ◽  
Pai 1

SummaryWe aimed to investigate significant correlations of insulin resistance with thrombotic factors in South Asians with stroke. Correlations of Homeostasis Model Assessment (HOMA)(as a surrogate of insulin resistance) were analysed with 6 thrombotic factors in 140 South Asian patients with a history of confirmed (by computerised tomography) ischaemic stroke. Age and sex adjusted HOMA was correlated to waist-hip ratio (r = 0.38, p = 0.0001), triglycerides (r = 0.22, p = 0.03), systolic blood pressure (r = 0.21, p = 0.04), tissue plasminogen activator (t-PA) (r = 0.22, p = 0.04); plasminogen activator inhibitor 1(PAI-1) (r = 0.26, p = 0.02); fibrinogen (r = 0.25, p = 0.02); and factor VII antigen (r = 0.21, p = 0.06). On regression analysis, with HOMA as dependent variable and significant correlates as independent variables in the model, HOMA was independently associated with PAI-1 antigen. There is extensive clustering of metabolic and thrombotic factors with insulin resistance in South Asian patients with ischaemic stroke, which may contribute to high prevalence of vascular disease in this population.

Plasminogen activator inhibitor-1 modulates adipocyte differentiation

2006 ◽  
Vol 290 (1) ◽  
pp. E103-E113 ◽  
Author(s):  
Xiubin Liang ◽  
Talerngsak Kanjanabuch ◽  
Su-Li Mao ◽  
Chuan-Ming Hao ◽  
Yi-Wei Tang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Mrna Expression ◽  
Glucose Uptake ◽  
Plasminogen Activator ◽  
Adipocyte Differentiation ◽  
Plasminogen Activator Inhibitor ◽  
Plasmin Activity ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor ◽  
Pai 1

Increased plasminogen activator inhibitor-1 (PAI-1) is linked to obesity and insulin resistance. However, the functional role of PAI-1 in adipocytes is unknown. This study was designed to investigate effects and underlying mechanisms of PAI-1 on glucose uptake in adipocytes and on adipocyte differentiation. Using primary cultured adipocytes from PAI-1+/+ and PAI-1−/− mice, we found that PAI-1 deficiency promoted adipocyte differentiation, enhanced basal and insulin-stimulated glucose uptake, and protected against tumor necrosis factor-α-induced adipocyte dedifferentiation and insulin resistance. These beneficial effects were associated with upregulated glucose transporter 4 at basal and insulin-stimulated states and upregulated peroxisome proliferator-activated receptor-γ (PPARγ) and adiponectin along with downregulated resistin mRNA in differentiated PAI-1−/− vs. PAI-1+/+ adipocytes. Similarly, inhibition of PAI-1 with a neutralizing anti-PAI-1 antibody in differentiated 3T3-L1 adipocytes further promoted adipocyte differentiation and glucose uptake, which was associated with increased expression of transcription factors PPARγ, CCAAT enhancer-binding protein-α (C/EBPα), and the adipocyte-selective fatty acid-binding protein aP2, thus mimicking the phenotype in PAI-1−/− primary adipocytes. Conversely, overexpression of PAI-1 by adenovirus-mediated gene transfer in 3T3-L1 adipocytes inhibited differentiation and reduced PPARγ, C/EBPα, and aP2 expression. This was also associated with a decrease in urokinase-type plasminogen activator mRNA expression, decreased plasmin activity, and increased collagen I mRNA expression. Collectively, these results indicate that absence or inhibition of PAI-1 in adipocytes protects against insulin resistance by promoting glucose uptake and adipocyte differentiation via increased PPARγ expression. We postulate that these PAI-1 effects on adipocytes may, at least in part, be mediated via modulation of plasmin activity and extracellular matrix components.

Reduction in Factor VII, Fibrinogen and Plasminogen Activator Inhibitor-1 Activity after Surgical Treatment of Morbid Obesity

1992 ◽  
Vol 68 (04) ◽  
pp. 396-399 ◽  
Author(s):  
J N Primrose ◽  
J A Davies ◽  
C R M Prentice ◽  
R Hughes ◽  
D Johnston
Keyword(s):  
Morbid Obesity ◽  
Surgical Treatment ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Factor Vii ◽  
Clot Lysis ◽  
Plasminogen Activator Inhibitor 1 ◽  
Platelet Factor ◽  
Activator Inhibitor ◽  
Pai 1

SummaryThe aim of this study was to determine the effects of the surgical treatment of morbid obesity on some aspects of haemostatic and fibrinolytic function. Measurement of haemostatic and fibrinolytic factors was performed before and again 6 and 12 months after operation in 19 patients suffering from morbid obesity. Surgical treatment resulted in a mean decrease in body weight of 50 kg at 6 months and 64 kg at 12 months. Weight loss was accompanied at 12 months by significant reductions in median (interquartile range) concentrations of serum cholesterol from 5.3 (4.5–6.2) mmol/1 to 3.6 (2.9–4.6) mmol/1; factor VII from 113 (92–145)% of normal to 99 (85–107)%; of fibrinogen from 3.5 (3–9.3) g/1 to 2.8 (2.4–3.8) g/1; and of plasminogen activator inhibitor-1 (PAI-1) activity from 21 (11–30) IU/ml to 6.3 (5–10) IU/ml. The decrease in PAI-1 activity probably accounted for a significant reduction in euglobulin clot lysis time. Tissue plasminogen activator activity was undetectable in most patients pre-operatively but increased slightly after 1 year to 110 (100–204) mIU/ml. There were no significant changes in plasma levels of KCCT, factor VIII, von Willebrand factor antigen, alpha-2-antiplasmin, antithrombin III, protein C antigen, beta thromboglobulin, platelet factor 4, fibrinopeptide A or platelet count. These findings provide support for the hypothesis that the surgical treatment of morbid obesity may have a long-term beneficial effect on mortality from cardiovascular and thromboembolic disease.

PAI-1 gene 4G/5G polymorphism, cytokine levels and their relations with metabolic parameters in obese children

2008 ◽  
Vol 99 (02) ◽  
pp. 352-356 ◽  
Author(s):  
Muammer Yuce ◽  
Ayse Yazici ◽  
Hasibe Verdi ◽  
F. Belgin Ataç ◽  
Sibel Kinik ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Plasminogen Activator Inhibitor ◽  
Control Group ◽  
Model Assessment ◽  
Obese Children ◽  
Plasminogen Activator Inhibitor 1 ◽  
Necrosis Factor Alpha ◽  
Pai 1

SummaryObesity is associated with the changes of plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor-alpha (TNFα) and transforming growth factor beta (TGFβ) levels. However, the precise effect of the 4G allele on obesity is still contradictory. Here, we aimed to elucidate the role of the 4G/5G polymorphism of the PAI-1 gene on the PAI-1 level and determine the associations between cytokines, glucose and lipid metabolism parameters in obese children. Thirty-nine obese children (mean age 11.4 ± 3.3 years) and 38 age-matched healthy control group (mean age 10.3 ± 3.5 years) were included in the study. In all cases, serum levels of glucose, lipid and insulin were measured, homeostasis model assessment of insulin resistance (HOMAIR) was calculated, and 4G/5G polymorphism of PAI-1 gene, plasma PAI-1 level and serum TNFα and TGFβ levels were studied. The mean relative body mass index (BMI) and HOMA-IR score, VLDL,TG, insulin, PAI-1,TNFα levels were higher, and HDL and TGFβ levels were lower in the obese group. The frequency of the 4G/4G genotype was considerably higher in obese children than in controls. Also, a positive correlation was found between PAI-1 and TNFα levels, and relative BMI, HOMA-IR score, insulin,TG, HDL levels. TGFβ was inversely correlated only with relative BMI. There was no correlation among three cytokines. In conclusion, childhood obesity contributes to higher PAI-1 andTNFα and lowerTGFβ levels. Especially PAI-1 andTNFα accompany insulin resistance and dyslipidemia.

scholarly journals Investigation of plasminogen activator inhibitor-1 (PAI-1) levels in patients diagnosed with polycystic ovary syndrome

2021 ◽  
Vol 3 (1) ◽  
pp. 6-9
Author(s):  
İhsan Bağlı ◽  
Mert Küçük
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Plasminogen Activator ◽  
Polycystic Ovary ◽  
Plasminogen Activator Inhibitor ◽  
Model Assessment ◽  
Plasminogen Activator Inhibitor 1 ◽  
Ovary Syndrome ◽  
Pcos Group ◽  
Activator Inhibitor ◽  
Pai 1

Objective:The aim of this study was to investigate the plasma levels of plasminogen activator inhibitor -1 (PAI-1) known as a potent inhibitor of fibrinolysis in women with polycystic ovary syndrome (PCOS) and compare with health controls. Methods: Forty women with PCOS diagnosed using 2003 revised Rotterdam criteria and 40 healthy women who attended to Adnan Menderes University Department of Obstetrics and Gynecology between July-October 2013 were recruited to this prospective study. We noted all participant’s demographic features, calculated body mass index (BMI), waist hip ratio (WHR), and measured blood pressures. We performed modified Ferriman-Gallwey Score (mFGS) and calculated Luteinizing hormone (LH)/Follicle stimulating hormone (FSH) ratio and homeostatic model assessment insulin resistance (HOMA-IR) of participants. PAI-1 levels were measured by using the Human PAI-1 Elisa test. We used the student T test and Mann-Whitney U test as statistical methods. A p-value less than 0.05 was considered statistically significant. Results: We found PAI-1 levels, fasting insulin levels, HOMA-IR index, BMI significantly higher in the PCOS group compared with the control group. Mean age of the participants was found lower in the PCOS group. Between the groups we found no statistically significant differences in terms of the LH/FSH ratio, fasting glucose, dehydroepiandrosterone and testosterone levels.

scholarly journals Combined but not single treatment with ethinylestradiol/levonorgestrel and spironolactone reduces plasminogen activator inhibitor-1 in insulin-resistant ovariectomised rats

2019 ◽  
Vol 20 (4) ◽  
pp. 147032031989593
Author(s):  
Adeyanju Oluwaseun Aremu ◽  
Dibia Chinaza Lilian ◽  
Soladoye Ayodele Olufemi ◽  
Olatunji Lawrence Aderemi
Keyword(s):  
Plasminogen Activator ◽  
Density Lipoprotein ◽  
Plasminogen Activator Inhibitor ◽  
Dependent Manner ◽  
Model Assessment ◽  
Plasminogen Activator Inhibitor 1 ◽  
Insulin Resistant ◽  
Ovx Rats ◽  
Activator Inhibitor ◽  
Pai 1

Objective: Increased circulating level of plasminogen activator inhibitor-1 (PAI-1) is associated with menopausal oestrogen deficiency. We therefore hypothesised that the combined oral contraceptive (COC) with spironolactone (SPL) improves insulin resistance (IR) in ovariectomised (OVX) rats by reducing circulating PAI-1. Methods: Twelve-week-old female Wistar rats were divided into sham-operated (SHM), OVX, OVX+SPL (0.25 mg/kg), COC (1.0 µg ethinylestradiol and 5.0 µg levonorgestrel) and OVX+COC+SPL rats treated with COC and SPL daily for eight weeks. IR was assessed by homeostatic model assessment of IR (HOMA-IR). Results: Data showed that OVX rats had a higher HOMA-IR value that is associated with increased visceral adiposity, triglycerides (TG), total cholesterol/high-density lipoprotein cholesterol (HDL-C), TG/HDL-C, plasma insulin, GSK-3, corticosterone and decreased 17β-oestradiol. However, these effects were attenuated in OVX+COC, OVX+SPL and OVX+COC+SPL rats compared to OVX rats. OVX rats had lower PAI-1 than SHM rats, whereas the beneficial effect on IR and other parameters by COC or SPL was accompanied with increased PAI-1. Improvement of IR and other parameters with combined COC and SPL in OVX rats was accompanied with reduced PAI-1. Conclusion: Taken together, COC or SPL improves IR independent of PAI-1, whereas a combination of COC and SPL in OVX rats ameliorates IR in a PAI-1-dependent manner.

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.

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