scholarly journals Impact of a Lifestyle Program on Vascular Insulin Resistance in Metabolic Syndrome Subjects: The RESOLVE Study

2015 ◽  
Vol 100 (2) ◽  
pp. 442-450 ◽  
Author(s):  
Agnes Vinet ◽  
Philippe Obert ◽  
Frederic Dutheil ◽  
Lamine Diagne ◽  
Robert Chapier ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Lifestyle Intervention ◽  
Vascular Dysfunction ◽  
Plasminogen Activator Inhibitor ◽  
Microvascular Dysfunction ◽  
Plasminogen Activator Inhibitor 1 ◽  
Reactive Protein ◽  
Lifestyle Program ◽  
Insulin Dependent ◽  
Pai 1

Abstract Context and Objective: Impaired insulin-dependent vasodilation might contribute to microvascular dysfunction of metabolic syndrome (MetS). The aims of this study were to assess the insulin vasoreactivity in MetS, and to evaluate the effects of a lifestyle program. Design, Setting, Participants, and Outcome Measures: Laser Doppler measurements were used to assess cutaneous blood flux (CBF) and flowmotion in response to iontophoresis of insulin and acetylcholine (ACh) in 38 MetS and 18 controls. Anthropometric, plasma insulin, glycemia, and inflammatory markers were measured. MetS subjects (n = 24) underwent a 6-month lifestyle intervention (M6) with a 3-week residential program (D21). Results: The absolute and relative peak insulin and ACh CBF were significantly higher in controls than in MetS subjects. Significant inverse correlations were found between peak insulin CBF and glycemia, insulin and glycated hemoglobin, active plasminogen activator inhibitor-1 (PAI-1), C-reactive protein (CRP), and IL-6. With respect to flowmotion, MetS subjects showed lower values in total spectrum CBF and in all its components (except respiratory one). At D21 and M6, peak insulin CBF increased and was no longer different from control values whereas peak ACh CBF did not change. From D21, all the different components and the total CBF spectrum became similar to the control values. The changes in peak insulin CBF and in endothelial component between M6 and baseline were inversely correlated with the change in CRP and PAI-1. Conclusions: The local vasodilatory effects to insulin and its overall flowmotion are impaired in MetS subjects in relation to inflammation. The lifestyle intervention reversed this insulin-induced vascular dysfunction in parallel to decreased inflammation level.

scholarly journals Association among Fibrinolytic Proteins, Metabolic Syndrome Components, Insulin Secretion, and Resistance in Schoolchildren

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Jin-Shuen Chen ◽  
Chung-Ze Wu ◽  
Nain-Feng Chu ◽  
Li-Chien Chang ◽  
Dee Pei ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Insulin Secretion ◽  
Plasminogen Activator ◽  
High Sensitivity ◽  
Plasminogen Activator Inhibitor ◽  
Normal Group ◽  
Plasminogen Activator Inhibitor 1 ◽  
Reactive Protein ◽  
Fibrinolytic Proteins ◽  
Pai 1

We investigated the role of urokinase plasminogen activator (uPA) and its soluble receptors (suPAR) and plasminogen activator inhibitor-1 (PAI-1) in metabolic syndrome (MetS) components, insulin secretion, and resistance in schoolchildren. We enrolled 387 children, aged 10.3 ± 1.5 years, in Taipei. Anthropometry, fibrinolytic proteins, MetS components, insulin secretion, and resistance were measured. Subjects were divided into normal, overweight, and obese groups. Finally, the relationship between fibrinolytic proteins and metabolic syndrome in boys and girls was analyzed. In boys, PAI-1 was positively associated with body mass index (BMI) percentile, hypertriglyceride, insulin secretion, and resistance. In girls, PAI-1 was positively associated with obesity, hypertriglyceridemia, and insulin secretion. In girls, uPA was positively associated with insulin secretion. suPAR was positively associated with high-sensitivity C-reactive protein in both boys and girls, and with BMI percentile and body fat in girls. The obese boys had higher suPAR and PAI-1 levels than the normal group. The obese girls had higher uPA, suPAR, and PAI-1 than the normal group. Boys and girls with MetS had higher PAI-1. Fibrinolytic proteins, especially PAI-1, are associated with MetS components and insulin secretion in children. Fibrinolytic proteins changes were more likely to occur in girls than in boys.

scholarly journals Microinflammation Factors in the Common Diseases of the Heart and Kidneys

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Danijela Tasic ◽  
Sonja Radenkovic ◽  
Gordana Kocic ◽  
Marina Deljanin Ilic ◽  
Aleksandra Ignjatovic
Keyword(s):  
Kidney Diseases ◽  
Plasminogen Activator Inhibitor ◽  
Cardiorenal Syndrome ◽  
High Density Lipoproteins ◽  
Control Group ◽  
C Reactive Protein ◽  
Plasminogen Activator Inhibitor 1 ◽  
Reactive Protein ◽  
Lipid Status ◽  
Pai 1

Aim. To determine levels of interleukin-8 (IL-8) and plasminogen activator inhibitor-1 (PAI-1) in different cardiorenal syndrome (CRS) modalities and to compare findings to some already investigated direct and indirect parameters of inflammation and atherosclerosis.Materials and Methods. Testing involved 114 examinees, divided into control and clinical groups suffering from different modalities and were formed according to the basis of a valid classification for CRS.Results. C-reactive protein (CRP) was significantly higher in all CRSs in comparison to the control groupP<0.05. PAI-1 in CRSs was statistically higher than in the control group. IL-8 was increased in all CRSs, and especially in CRS-5, where no significance was found. PAI-1 correlated with IL-8 in all CRSs, with significant value in CRS-2 and CRS-5. Correlation for PAI-1 and high-density lipoproteins (HDL) was found in CRS-4, while IL-8 was found to be related to CRP level in all CRSs, with significance only in CRS-1P<0.001.Conclusions. C-reactive protein, IL-8, and PAI-1 could be useful for clinical differentiation of chronic modalities of CRSs. Inflammation was the most pronounced in CRS-4. Lipid status parameters could be useful for differentiation of CRSs. Furthermore, HDL in chronic primary kidney diseases and triglycerides and total cholesterol in CRS-5 could be valuable.

scholarly journals Emerging Role of Endothelial and Inflammatory Markers in Preeclampsia

2009 ◽  
Vol 26 (3) ◽  
pp. 127-133 ◽  
Author(s):  
Menha Swellam ◽  
Nervana Samy ◽  
Susan Abdl Wahab ◽  
Mohamed Saeed Ibrahim
Keyword(s):  
Inflammatory Markers ◽  
Linear Regression Analysis ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
New Approach ◽  
Reactive Protein ◽  
Diagnostic Role ◽  
Activator Inhibitor ◽  
Pai 1

Objectives:Endothelial disturbance and excess inflammatory response are pathogenic mechanisms in pre-eclampsia (PE). Authors determine the clinical diagnostic role for thrombomodulin (TM), plasminogen activator inhibitor-1 (PAI-1) as endothelial markers and C-reactive protein (CRP), and interlukin-6 (IL-6) as inflammatory markers when tested independently or in combinations.Materials and methods:We conducted a retrospective study in a cohort of 185 women grouped as 80 women with PE, 55 normotensive pregnant and 50 healthy non-pregnant. Plasma levels of TM, PAI-1, CRP and IL-6 were examined using enzyme linked immunosorbent assays.Results:Median levels and the positivity rates for the investigated markers were higher in PE as compared to the other groups (P< 0.0001). Using linear regression analysis, the investigated markers were significantly correlated regarding healthy nonpregnantvsPE or normotensive pregnantvsPE. The sensitivity of PAI-1 was the highest (98%) among the tested biomarkers. Combination between the investigated markers revealed absolute sensitivity (100%) and reliable specificity especially when PAI-1 was combined with CRP at 83% specificity.Conclusions:Investigated endothelial and inflammatory markers revealed sensitive diagnostic test for PE. However, coupled combination between PAI-1 with CRP showed superior both sensitivity and specificity which represent a promising new approach for detection of PE.

scholarly journals Dynamics of Soluble Thrombomodulin and Circulating miRNAs in Patients with Atrial Fibrillation Undergoing Radiofrequency Catheter Ablation

2019 ◽  
Vol 25 ◽  
pp. 107602961985157
Author(s):  
Fuminori Namino ◽  
Munekazu Yamakuchi ◽  
Yasuhisa Iriki ◽  
Hideki Okui ◽  
Hitoshi Ichiki ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Plasminogen Activator Inhibitor ◽  
Clinical Markers ◽  
Blood Proteins ◽  
Plasminogen Activator Inhibitor 1 ◽  
Soluble Thrombomodulin ◽  
Reactive Protein ◽  
Before And After ◽  
Pai 1

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the world and has a high risk of thromboembolism. The most effective approach, catheter ablation, requires evaluation by electrocardiography. The aim of our study was to investigate novel clinical markers that predict restoration of sinus rhythm (SR) after catheter ablation. Seventy-eight consecutive patients with AF underwent catheter ablation and were separated into 2 groups: restored SR and recurrent AF. The levels of 4 blood proteins (serum or plasma) and 3 mature microRNAs (miRNAs) and their primary miRNAs (pri-miRNAs) in serum were measured before and after ablation, and the associations between each parameter were analyzed statistically. Soluble thrombomodulin (s-TM) and plasminogen activator inhibitor-1 (PAI-1) levels increased above baseline after ablation in both the restored SR (s-TM 11.55 [2.92] vs 13.75 [3.38], P < .001; PAI-1 25.74 [15.25] vs 37.79 [19.56], P < .001) and recurrent AF (s-TM 10.28 [2.78] vs 11.67 [3.37], P < .001; PAI-1 26.16 [15.70] vs 40.74 [22.55], P < .001) groups. Levels of C-reactive protein and asymmetric dimethylarginine were not significantly changed. Pri-miR-126 levels significantly decreased after ablation in the recurrent AF group, but the other miRNAs and pri-miRNAs did not. The measurement of s-TM and pri-miR-126 in blood was a useful tool to reflect the condition of AF patients with catheter ablation.

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.

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.

Environmental and Genetic Factors in Relation to Elevated Circulating Levels of Plasminogen Activator Inhibitor-1 in Caucasian Patients with Non-Insulin-Dependent Diabetes Mellitus

1995 ◽  
Vol 74 (03) ◽  
pp. 842-847 ◽  
Author(s):  
Michael W Mansfield ◽  
Max H Stickland ◽  
Peter J Grant
Keyword(s):  
Genetic Factors ◽  
Gene Promoter ◽  
Plasminogen Activator Inhibitor ◽  
Insulin Dependent Diabetes Mellitus ◽  
Dependent Diabetes Mellitus ◽  
Plasminogen Activator Inhibitor 1 ◽  
Insulin Dependent ◽  
Caucasian Patients ◽  
Activator Inhibitor ◽  
Pai 1

SummaryTo investigate the interaction of metabolic and genetic factors in relation to PAI-1, genotype was determined at a 4G/5G polymorphism in the PAI-1 gene promoter and at a Hind III RFLP of the PAI-1 gene in 189 Caucasian NIDDM patients. PAI-1 levels were equivalent in each genotype group and PAI-1 activity correlated with fasting insulin (r = 0.45), triglyceride (r = 0.39) body mass index (r = 0.44), cholesterol (r = 0.17) and glucose (r = 0.15). The regression slope (B) of PAI-1 activity on triglycerides was steeper in the 4G/4G group than the other two groups: 4G/4G B = 0.91, r = 0.62; 4G/5G B = 0.36, r = 0.27; 5G/5G B = 0.31, r = 0.29 (difference between slopes p = 0.02) and the association between PAI-1 activity and glucose remained only in the 4G/4G group (r = 0.35). These results confirm the association of PAI-1 levels with the features of insulin resistance and indicate that the association between PAI-1 levels and both triglyceride and glucose is influenced by genotype in the region of the PAI-1 gene promoter.

Abstract 179: Targeted Inhibition of Plasminogen Activator Inhibitor-1 Attenuates Weight Gain and Prevents Vascular Dysfunction Following a High Fat Diet

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Sadiya S Khan ◽  
Alexander Mackie ◽  
Lauren Beussink-Nelson ◽  
Christine E Kamide ◽  
Anne S Henkel ◽  
...  
Keyword(s):  
Weight Gain ◽  
Energy Expenditure ◽  
Plasminogen Activator ◽  
High Fat Diet ◽  
Vascular Dysfunction ◽  
Plasminogen Activator Inhibitor ◽  
High Fat ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor ◽  
Pai 1

Introduction: Elevated plasminogen activator inhibitor-1 (PAI-1) is associated with obesity, but there is controversy whether PAI-1 causes or is a consequence of obesity. We sought to determine whether targeted PAI-1 inhibition with a novel small molecule antagonist (TM5441) alters the development of obesity and/or obesity-induced vascular dysfunction in a diet-induced obesity model. Methods and Results: C57BL/6J mice were fed control, high fat diet (HFD), or high fat diet with TM5441 (HFD+TM5441) for 12 weeks. The HFD had marked weight gain (77±5%) as compared with control (32±2%). TM5441 significantly attenuated weight gain (49±8%, p=0.0075, Figure). HFD-induced hepatic triglyceride accumulation was attenuated by TM5441 (116±31 vs. 76±35 mg trig/g liver, p=0.03). Energy expenditure was reduced in the HFD compared to control (11.1±0.4 vs. 12.9±0.4 kcal/h/kg, p=0.005). However, HFD+TM5441 maintained a level of energy expenditure that was similar to control (13.2±0.6 kcal/h/kg, p=NS). The HFD group demonstrated higher systolic and diastolic blood pressure (141±3; 112±3 mm Hg) compared with control (122±7, 94±8; P<0.05 for both), while administration of TM5441 prevented diet-associated increase (120±6; 93±7 mm Hg, p=NS compared to control) at week 12. Pressure myography of mesenteric arteries in the HFD showed a significant rightward shift in the constrictor response to phenylephrine as compared to control (EC50: 14.5uM vs. 25.1uM, p=0.002). The HFD+TM5441 was similar to control (p=NS). Conclusions: Inhibition of PAI-1 with TM5441 attenuates weight gain, enhances energy expenditure, and prevents obesity-related vascular dysfunction in a murine model of obesity.

scholarly journals Circulating Concentrations of Monocyte Chemoattractant Protein-1, Plasminogen Activator Inhibitor-1, and Soluble Leukocyte Adhesion Molecule-1 in Overweight/Obese Men and Women Consuming Fructose- or Glucose-Sweetened Beverages for 10 Weeks

2011 ◽  
Vol 96 (12) ◽  
pp. E2034-E2038 ◽  
Author(s):  
Chad L. Cox ◽  
Kimber L. Stanhope ◽  
Jean Marc Schwarz ◽  
James L. Graham ◽  
Bonnie Hatcher ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Plasminogen Activator Inhibitor ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Plasminogen Activator Inhibitor 1 ◽  
Monocyte Chemoattractant Protein 1 ◽  
Reactive Protein ◽  
Sweetened Beverages ◽  
Activator Inhibitor ◽  
Pai 1

Abstract Context: Results from animal studies suggest that consumption of large amounts of fructose can promote inflammation and impair fibrinolysis. Data describing the effects of fructose consumption on circulating levels of proinflammatory and prothrombotic markers in humans are unavailable. Objective: Our objective was to determine the effects of 10 wk of dietary fructose or glucose consumption on plasma concentrations of monocyte chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1), E-selectin, intercellular adhesion molecule-1, C-reactive protein, and IL-6. Design and Setting: This was a parallel-arm study with two inpatient phases (2 wk baseline, final 2 wk intervention), conducted in a clinical research facility, and an outpatient phase (8 wk) during which subjects resided at home. Participants: Participants were older (40–72 yr), overweight/obese (body mass index = 25–35 kg/m2) men (n = 16) and women (n = 15). Interventions: Participants consumed glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 wk. Blood samples were collected at baseline and during the 10th week of intervention. Main Outcome Measures: Fasting concentrations of MCP-1 (P = 0.009), PAI-1 (P = 0.002), and E-selectin (P = 0.048) as well as postprandial concentrations of PAI-1 (P &lt; 0.0001) increased in subjects consuming fructose but not in those consuming glucose. Fasting levels of C-reactive protein, IL-6, and intercellular adhesion molecule-1 were not changed in either group. Conclusions: Consumption of fructose for 10 wk leads to increases of MCP-1, PAI-1, and E-selectin. These findings suggest the possibility that fructose may contribute to the development of the metabolic syndrome via effects on proinflammatory and prothrombotic mediators.

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.

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