scholarly journals Plasma Plasminogen Activator Inhibitor-1 Levels and Nonalcoholic Fatty Liver in Individuals With Features of Metabolic Syndrome

2008 ◽  
Vol 14 (3) ◽  
pp. 319-324 ◽  
Author(s):  
Gabriela de Larrañaga ◽  
Silvia Perés Wingeyer ◽  
Mabel Graffigna ◽  
Susana Belli ◽  
Karla Bendezú ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Body Mass Index ◽  
Fatty Liver ◽  
Hdl Cholesterol ◽  
Insulin Level ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor ◽  
Pai 1

Fatty liver represents the liver component of metabolic syndrome and may be involved in plasminogen activator inhibitor-1 (PAI-1) synthesis. We studied plasma PAI-1 levels and relationships with risk factors for metabolic syndrome, including fatty liver, in 170 patients. Liver ultrasound scan was performed on all patients, and a liver biopsy was performed on those patients with chronically elevated transaminase levels. Plasma PAI-1 levels correlated significantly ( P < .05) with body mass index, degree of steatosis, insulin resistance, insulin level, waist circumference, triglycerides, and high-density lipoprotein (HDL) -cholesterol. However, only body mass index (β = .455) and HDL-cholesterol (β = .293) remained predictors of PAI-1 levels. Liver biopsy revealed a significant correlation ( P < .05) between insulin resistance ( r = 0.381) or insulin level ( r = 0.519) and liver fibrosis. In patients presenting features of metabolic syndrome, plasma PAI-1 levels were mainly conditioned by the whole-body fat content.

Association of prothrombotic adipokine (plasminogen activator inhibitor-1) with TSH in metabolic syndrome: a case control study

2017 ◽  
Vol 0 (0) ◽  
Author(s):  
Ashok Kumar Ahirwar ◽  
Archana Singh ◽  
Anju Jain ◽  
Kirti Kaim ◽  
Shilpa Bhardwaj ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Thyroid Dysfunction ◽  
Case Control Study ◽  
Plasminogen Activator Inhibitor ◽  
Case Control ◽  
Plasminogen Activator Inhibitor 1 ◽  
The Mean ◽  
Activator Inhibitor ◽  
Pai 1 ◽  
Control Study

AbstractBackgroundMetabolic syndrome (MetS) involves a cluster of cardiovascular risk factors, including abnormal lipids, insulin resistance and hypertension. The aim of the present study is to investigate associations between thyroid profile and the pro-thrombotic mediator, plasminogen activator inhibitor-1 (PAI-1), in MetS and identify associated biochemical markers.Materials and methodsThe present study was a case control study and consisted of 50 diagnosed cases of MetS and 50 healthy volunteers as controls. MetS cases were further divided into two groups based on the presence and absence of subclinical hypothyroidism (SCH). Data collected included demographic profile, clinical history and routine lab investigation. Special investigations included the thyroid function test and serum PAI-1 levels.ResultsThe mean serum thyroid-stimulating hormone (TSH) levels were significantly higher in MetS cases as compared to controls (5.7 ± 1.2 mIU/L vs. 2.3 ± 1.6 mIU/L, p < 0.0001), although the mean triiodothyronine (TConclusionThe present study points towards the presence of thyroid dysfunction, in the form of subclinical hypothyroidism (SCH), in cases of MetS. In the presence of thyroid dysfunction, abnormal adipocytes may release adipokines, such as PAI-1, which lead to increased risk of thrombotic episodes in these patients. Hence, SCH should be appropriately managed.

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.

scholarly journals The 4G/5G Polymorphism in the Plasminogen Activator Inhibitor-1 Gene Is not Associated with Myocardial Infarction

1999 ◽  
Vol 82 (07) ◽  
pp. 115-120 ◽  
Author(s):  
C. J. M. Doggen ◽  
R. M. Bertina ◽  
V. Manger Cats ◽  
P. H. Reitsma ◽  
F. R. Rosendaal
Keyword(s):  
Myocardial Infarction ◽  
Plasminogen Activator ◽  
Hdl Cholesterol ◽  
Plasminogen Activator Inhibitor ◽  
Inverse Association ◽  
Plasminogen Activator Inhibitor 1 ◽  
Control Subjects ◽  
Activator Inhibitor ◽  
Pai 1 ◽  
Healthy Persons

SummarySeveral studies have found an association between high plasminogen activator inhibitor-1 (PAI-1) levels and myocardial infarction. Whether this is causal or a consequence of atherosclerosis or tissue damage, remains unclear. Homozygous carriers of the 4G allele of the 4G/5G polymorphism in the PAI-1 gene have higher PAI-1 levels compared to carriers of the 5G allele in healthy persons in some studies, but not all. If PAI-1 levels are causally related to myocardial infarction, one would expect more homozygous carriers of the 4G allele among patients, provided that these carriers have high PAI-1 levels among healthy persons in that population. We investigated the distribution of this polymorphism in the “Study of Myocardial Infarctions Leiden” (SMILE), including 331 men with a myocardial infarction and 302 control subjects and measured PAI-1 antigen levels among the latter. Secondly, we looked into the association of cardiovascular risk factors with PAI-1 levels.We did not find an increase in risk of myocardial infarction in carriers of the 4G allele. Neither did we find an association, nor a trend, between the 4G/5G polymorphism and PAI-1 antigen levels in control subjects. Controls with obesity, hypertension, or who smoked had significant higher PAI-1 antigen levels compared with persons without these factors. High cholesterol and triglyceride levels were also associated with high PAI-1 antigen levels, and HDL-cholesterol levels showed an inverse association.We conclude that the 4G/5G polymorphism in the PAI-1 gene is not associated with the risk of myocardial infarction. As we did not find any association between this polymorphism and PAI-1 antigen levels in healthy persons, we cannot draw any conclusions about the causality of PAI-1 itself for myocardial infarction.

scholarly journals Assessment of plasminogen activator inhibitor-1 in obese Egyptian children

2020 ◽  
Vol 68 (1) ◽  
Author(s):  
Marwa Farouk Mira ◽  
Ghada Mohammad Anwar ◽  
Azza Mohamed Sarry EL-Din ◽  
Safinaz Mohammed Megahed
Keyword(s):  
Metabolic Syndrome ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Anthropometric Measurements ◽  
Obese Children ◽  
Plasminogen Activator Inhibitor 1 ◽  
Skin Fold Thickness ◽  
Skin Fold ◽  
Activator Inhibitor ◽  
Pai 1

Abstract Background Plasminogen activator inhibitor-1 (PAI-1) is mainly produced in the liver and in the adipose tissue. Normal fibrin clearance mechanisms were found to be affected by high plasma PAI-1 levels and thus increases risk of thrombosis. The aim of the current study was to expound the childhood obesity effect on circulating PAI-1 and interpret the relation of PAI-1 to metabolic syndrome. This cross-sectional study was conducted on 43 obese children following in the Children Hospital and compared to 44 healthy sex- and age-matched controls. All recruited cohort are subjected to anthropometric measurements: weight, height, BMI, waist circumference, hip circumference, and skin fold thickness (biceps, triceps, and subscapular), and laboratory investigations in the form of lipid profile, fasting blood sugar, fasting insulin, insulin resistance estimated by HOMA-IR, and plasminogen activator inhibitor-1. Results The level of plasminogen activator inhibitor-1 in the obese group was significantly higher than that in the control group (47.98 ± 17.42 vs. 28.00 ± 11.35 respectively). PAI-1 showed positive significant correlation to anthropometric measurements: BMI (p = 0.000), weight (p = 0.000), biceps skin fold thickness (p = 0.04), triceps skin fold thickness (p = 0.4), and subscapular skin fold thickness (p = 0.04). Also, a significant positive correlation was found between PAI-1 and systolic (p = 0.000) and diastolic blood pressure (p = 0.04). Positive correlations were found between PAI-1 and cholesterol (p = 0.000), triglycerides (p = 0.02), LDL-c (p = 0.000), insulin (p = 0.000), and HOMA-IR (r = 0.5, p = 0.02). Conclusion Fat mass accumulation is related to high PAI-1 levels, which might in turn contribute to cardiovascular risk. Plasminogen Activator Inhibitor-1 is a good predictive test for metabolic syndrome in obese children.

scholarly journals Plasminogen Activator Inhibitor-1 Deficiency Ameliorates Insulin Resistance and Hyperlipidemia But Not Bone Loss in Obese Female Mice

Endocrinology ◽  
2014 ◽  
Vol 155 (5) ◽  
pp. 1708-1717 ◽  
Author(s):  
Yukinori Tamura ◽  
Naoyuki Kawao ◽  
Masato Yano ◽  
Kiyotaka Okada ◽  
Osamu Matsuo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Bone Loss ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Female Mice ◽  
Glucose And Lipid Metabolism ◽  
Obese Female ◽  
Tnf Α ◽  
Activator Inhibitor ◽  
Pai 1

We previously demonstrated that plasminogen activator inhibitor-1 (PAI-1), an inhibitor of fibrinolysis, is involved in type 1 diabetic bone loss in female mice. PAI-1 is well known as an adipogenic factor induced by obesity. We therefore examined the effects of PAI-1 deficiency on bone and glucose and lipid metabolism in high-fat and high-sucrose diet (HF/HSD)-induced obese female mice. Female wild-type (WT) and PAI-1–deficient mice were fed with HF/HSD or normal diet for 20 weeks from 10 weeks of age. HF/HSD increased the levels of plasma PAI-1 in WT mice. PAI-1 deficiency suppressed the levels of blood glucose, plasma insulin, and total cholesterol elevated by obesity. Moreover, PAI-1 deficiency improved glucose intolerance and insulin resistance induced by obesity. Bone mineral density (BMD) at trabecular bone as well as the levels of osterix, alkaline phosphatase, and receptor activator of nuclear factor κB ligand mRNA in tibia were decreased by HF/HSD in WT mice, and those changes by HF/HSD were not affected by PAI-1 deficiency. HF/HSD increased the levels of plasma TNF-α in both WT and PAI-1–deficient mice, and the levels of plasma TNF-α were negatively correlated with trabecular BMD in tibia of female mice. In conclusion, we revealed that PAI-1 deficiency does not affect the trabecular bone loss induced by obesity despite the amelioration of insulin resistance and hyperlipidemia in female mice. Our data suggest that the changes of BMD and bone metabolism by obesity might be independent of PAI-1 as well as glucose and lipid metabolism.

The Effect of Cigarette-Smoking on Cardiovascular Risk Factors: a Study of Monozygotic Twins Discordant for Smoking

1996 ◽  
Vol 75 (01) ◽  
pp. 014-018 ◽  
Author(s):  
Giliola Calori ◽  
Armando D’Angelo ◽  
Patrizia Della Valle ◽  
Giacomo Ruotolo ◽  
Luigi Ferini-Strambi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cigarette Smoking ◽  
Blood Cell ◽  
Hdl Cholesterol ◽  
Plasminogen Activator Inhibitor ◽  
Vascular Lesions ◽  
Plasminogen Activator Inhibitor 1 ◽  
Cell Counts ◽  
Activator Inhibitor ◽  
Pai 1

SummaryThe association of cigarette smoking with the development of occlusive vascular disease is firmly established. Unfavourable changes in a series of variables held independent risk factors for the development of vascular lesions (HDL-cholesterol, haematocrit, white blood cell count, fibrinogen and plasminogen activator inhibitor-1 (PAI-1)) are thought to be directly influenced by cigarette smoking. However, the role played by the genotype in the effect of smoking on the above parameters has not been investigated. To control the genotype, we studied the relationship between cigarette smoking and a series of cardiovascular risk factors in 27 monozygotic twin pairs (7 male and 20 female pairs, mean age ± SD: 47.4 ± 12.9 yrs) with a life-long discordance for smoking. Smoking twins had a life-long dose of smoking (Brickman index) of 287.3 ± 241.5. Body mass index, blood pressure, haematocrit, haemoglobin and red blood cell counts, total cholesterol levels and the acute phase reactants α-acid glycoprotein and C-reactive protein were similar in smokers and non-smokers. Triglyceride was higher by 12.6% (9.5-35%, 95% confidence interval, p = 0.02) and HDL-cholesterol lower by 7.5% (0.2-15%, p = 0.04) in the smoking co-twins, who also had 8.4 % (-0.2-17%, p = 0.06) higher white blood cell counts and 4.1% (1.2-7%, p <0.01) larger mean platelet volume. There was no significant difference in clottable fibrinogen (by two methods) or in the activity of plasminogen activator inhibitor-1 between the two groups, nor was the within-pair difference in these parameters related to the smoking dose. Echo-doppler examination of the carotid arteries of 24 twin pairs showed mostly minor atherosclerotic lesions in 46% and 42% of the smoking and non-smoking co-twins. After adjustment for age, systolic blood pressure and platelet count and volume were the only variables significantly associated to the presence of vascular lesions. Cigarette smoking is associated with an atherogenic lipid profile and with changes in platelets and white cells potentially reflecting endothelial cell damage. When controlling the genotype, fibrinogen and PAI-1 activity levels did not seem directly influenced by cigarette smoking.

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>

Role of Gender and Genetic Variance in Plasminogen Activator Inhibitor-1 Secretion from Human Adipose Tissue

2000 ◽  
Vol 83 (02) ◽  
pp. 304-308 ◽  
Author(s):  
Hans Wahrenberg ◽  
Per Eriksson ◽  
Peter Arner ◽  
Vanessa Van Harmelen
Keyword(s):  
Body Mass Index ◽  
Adipose Tissue ◽  
Gender Difference ◽  
Subcutaneous Adipose Tissue ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Plasma Triglycerides ◽  
Subcutaneous Adipose ◽  
Activator Inhibitor ◽  
Pai 1

SummaryGender and the 4G/5G polymorphism in the plasminogen activator inhibitor 1 (PAI-1) gene are believed to play a role in the regulation of plasma PAI-1 activity. Adipose tissue has been found to be an important source of PAI-1. The possible influence of gender and the 4G/5G polymorphism in the PAI-1 gene on PAI-1 secretion from abdominal subcutaneous adipose tissue was investigated in 59 women and 32 men. The subjects were apparantly healthy, although they differed markedly inter-individually in body mass index (21-53 kg/m2). The 4G/5G polymorphism did not influence the adipose secretion rate of PAI-1 or plasma PAI-1 activity. There was no gender difference in the adipose secretion of PAI-1. In multiple regression, including body mass index (BMI), waist-to-hip ratio (WHR), plasma insulin and plasma triglycerides as the independent and adipose PAI-1 secretion as the dependent variable, only BMI and plasma triglycerides correlated independently with adipose PAI-1 secretion (r = 0.54, p <0.05; r = 0.51, p <0.05, respectively). Men had a two times higher plasma PAI-1 activity than women (p <0.05). This gender difference was mainly due to gender differences in WHR. In multiple regression analysis, BMI and WHR were identified to be independently correlated with plasma PAI-1 activity (r = 0.60, p <0.05; r = 0.52, p = 0.01, respectively). In conclusion, neither gender nor the 4G/5G polymorphism in the PAI-1 gene are associated with secretion of PAI-1 from abdominal subcutaneous adipose tissue.

The 4G/5G Sequence Polymorphism in the Promoter of Plasminogen Activator Inhibitor-1 (PAI-1) Gene: Relationship to Plasma PAI-1 Level in Venous Thromboembolism

1998 ◽  
Vol 79 (05) ◽  
pp. 975-979 ◽  
Author(s):  
Mojca Stegnar ◽  
Pavel Uhrin ◽  
Polona Peternel ◽  
Alenka Mavri ◽  
Barbara Salobir-Pajnič ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Venous Thromboembolism ◽  
Plasminogen Activator ◽  
Body Mass ◽  
Plasminogen Activator Inhibitor ◽  
Healthy Controls ◽  
Metabolic Factors ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor ◽  
Pai 1

SummaryImpaired fibrinolysis due to increased plasminogen activator inhibitor-1 (PAI-1) is observed in up to 40% of patients with venous thromboembolism and might be causally related to the disease. There is evidence that genetic variations in the promoter of the PAI-1 gene and metabolic factors contribute to increased plasma PAI-1 levels.A single nucleotide insertion/deletion (4G/5G) polymorphism in the promoter region of the PAI-1 gene and metabolic factors were studied in 158 unrelated patients below the age of 61 years (43 ± 11 years, mean ± standard deviation) with history of objectively confirmed venous thromboembolism and in 145 apparently healthy controls.Patients had on average two times higher PAI activity (11.9 vs. 6.1 IU/ml) and by 40% higher PAI-1 antigen (14.8 vs. 10.7 ng/ml) than healthy controls, and also higher body mass index, lipid levels, fasting glucose and insulin. Patients differed significantly from healthy controls neither in the frequency of the 4G and 5G alleles (0.57/0.43 in patients and 0.52/0.48 in controls) nor in the distribution of the 4G/5G genotypes. Possession of the 4G/4G or the 4G/5G genotype did not increase relative risk for venous thromboembolic disease and the distribution of the 4G/5G genotypes was neither associated with recurrent nor with spontaneous disease. In patients association between the 4G/5G genotypes and PAI activity (adjusted for body mass index, triglyceride and glucose level) was observed, with the highest PAI activity values in the 4G/4G genotype (14.6 IU/ml), intermediate in the 4G/5G genotype (13.3 IU/ml) and the lowest in the 5G/5G genotype (5.2 IU/ml, all values means). Association between PAI activity and triglyceride level was the strongest in the 4G/4G genotype (correlation coefficient r = 0.47, p <0.01) and the weakest in the 5G/5G genotype (r = -0.04, not significant).In conclusion, the present case-control study shows an association between the 4G/5G polymorphism in the promoter of the PAI-1 gene and plasma PAI-1 levels in patients with venous thromboembolism. Similar distribution of the 4G/5G genotypes in patients and healthy controls suggests that this genetic variation by itself is not a major risk factor for venous thromboembolism.

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