Abstract 43: Association of Plasminogen Activator Inhibitor-1 with Prevalent and Incident Obesity is Independent of Inflammatory Markers: The Multi-Ethnic Study of Atherosclerosis (MESA)

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Sadiya S Khan ◽  
Donald M Lloyd-Jones ◽  
Cheelin Chan ◽  
Kiang Liu ◽  
Mary Cushman ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Inflammatory Markers ◽  
Smoking Status ◽  
Plasminogen Activator Inhibitor ◽  
Cox Proportional Hazards ◽  
Plasminogen Activator Inhibitor 1 ◽  
Ethnic Study ◽  
Activator Inhibitor ◽  
Pai 1

Background: In experimental animal models, deficiency of plasminogen activator inhibitor-1 (PAI-1) protects against development of obesity. In addition, elevated circulating levels of PAI-1 are associated in cross-sectional studies with prevalent obesity in humans. However, no studies have investigated the prospective association between PAI-1 and incident obesity. Methods: Plasma PAI-1 levels were measured in a random sample of men and women at baseline (2000-2002) in the Multi-Ethnic Study of Atherosclerosis. Obesity was defined as body mass index (BMI) > 30kg/m2. Incident obesity was identified at four follow-up exams (2002-2011) among those who were not obese at baseline. Logistic regression was used to examine the odds ratios (OR) and 95% confidence intervals (CI) of prevalent obesity at baseline. Cox proportional hazards regression was used to estimate hazard ratios (HR) for time to incident obesity. The covariates used for adjustment included baseline demographics (age, race, sex, center), lifestyle risk factors (physical activity, dietary energy intake, smoking status, alcohol consumption, education), and inflammatory markers (CRP and IL-6). Results: In 839 participants mean age was 59 years old; 59% and 47% of the cohort were female and white, respectively. At baseline, each standard deviation (SD) increase in log(PAI-1) level was associated with an odds ratio (OR) for adjusted prevalent obesity of 2.70 (95% CI: 2.21 - 3.30, p<0.001. This association remained significant after further adjustment for IL-6 and CRP with OR 2.39 (95% CI: 1.94-2.94, p<0.001). Over a median follow-up of 8.5 years, 16% of participants developed obesity. The multivariable adjusted hazard ratio for incident obesity was 1.36 (95% CI 1.09-1.69, p<0.001) per 1 SD increase in log(PAI-1). (Table). Conclusions: Elevated PAI-1 levels are associated with prevalent and incident obesity. These findings are consistent with results from murine studies and provide evidence suggesting a potential role of PAI-1 in the pathogenesis of obesity.

Plasminogen activator inhibitor-1 and outcome after femoropopliteal angioplasty: analysis of genotype and plasma levels

2003 ◽  
Vol 90 (10) ◽  
pp. 717-723 ◽  
Author(s):  
Martin Schillinger ◽  
Markus Exner ◽  
Schila Sabeti ◽  
Christine Mannhalter ◽  
Erich Minar ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Plasma Levels ◽  
Gene Promoter ◽  
Plasminogen Activator Inhibitor ◽  
Cox Proportional Hazards ◽  
Nucleotide Position ◽  
Plasminogen Activator Inhibitor 1 ◽  
Late Restenosis ◽  
Activator Inhibitor ◽  
Pai 1

SummaryPlasminogen activator inhibitor-1 (PAI-1) is suggested to be involved in the pathophysiology of early thrombosis and late restenosis after percutaneous transluminal angioplasty (PTA). The role of the PAI-1 promoter genotype in this context is indeterminate. We investigated the association of the (4G/5G) polymorphism at nucleotide position (–675) in the PAI-1 gene promoter, PAI-1 plasma levels, and postangioplasty outcome after femoropopliteal PTA.We studied 251 consecutive patients who underwent femoropopliteal PTA. In a subgroup of 86 patients PAI-1 plasma levels at baseline,8,24 and 48 hours postintervention were measured and correlated to the genotype. Patients were followed for early thrombosis and the late restenosis (≥50%) within 12 months. Multivariate Cox proportional hazards analysis was performed to assess the association between the PAI-1 genotype and PTA failure.Results show that the PAI-1 genotype was neither associated with PAI-1 plasma levels (p=0.40) nor the change of PAI-1 from baseline to 8 (p=0.39), 24 (p=0.86) and 48 hours (p=0.89). Three out of 35 homozygous (4G/4G) patients (9%) had early thrombotic reocclusions, compared to two out of 153 heterozygous (4G/5G) patients (1%) and none of the 63 homozygous (5G/5G) patients (p=0.007). Restenosis after median 5 months (interquartile range 3 to 9) was found in 117 patients (42%), without significant association between the PAI-1 genotype and late postangioplasty failure (Log Rank p=0.95).We can conclude that carriers of the 4G allele exhibited a higher frequency of early thrombotic reocclusions after percutaneous angioplasty. However, the PAI-1 gene promoter polymorphism (4G/5G) was not associated with PAI-1 plasma levels or late postangioplasty restenosis.

Abstract 9379: Higher Levels of Plasminogen-Activator Inhibitor 1 Are Associated with Progression of Coronary Artery Calcification in Middle-Aged Women: The Study of Women’s Health Across the Nation (SWAN) Heart Study

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Norman C Wang ◽  
Karen A Matthews ◽  
Emma J Barinas-Mitchell ◽  
Chung-Chou H Chang ◽  
Samar R El Khoudary
Keyword(s):  
Coronary Artery ◽  
Plasminogen Activator ◽  
Coronary Artery Calcification ◽  
Density Lipoprotein ◽  
Plasminogen Activator Inhibitor ◽  
Lipoprotein Cholesterol ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor ◽  
Pai 1

Introduction: Relationships of inflammatory and hemostatic biomarkers with progression of coronary artery calcification (CAC) in asymptomatic women are unknown. Hypothesis: We assessed the hypothesis that C-reactive protein (CRP), fibrinogen, plasminogen-activator inhibitor 1 (PAI-1), and tissue plasminogen activator antigen (tPA-ag) were associated with CAC progression in women free of known coronary heart disease (CHD) and stroke. Methods: CRP, fibrinogen, PAI-1, and tPA-ag were measured in SWAN Heart participants from the Pittsburgh and Chicago sites at baseline. CAC was obtained by CT scans and quantified by the Agatston score at baseline and after 2.3±0.5 years of follow-up. Significant CAC progression was defined as present if 1) CAC score was >0 at follow-up in subjects with CAC score = 0 at baseline, 2) annualized change in CAC score was ≥10 in subjects with 0<CAC score<100 at baseline, and 3) annualized percent change in CAC score was ≥10% in subjects with CAC score ≥100 at baseline. Univariable and multivariable logistic regression were used for statistical analyses. The novel biomarkers were log-transformed. Baseline CAC was transformed as log(CAC+1). Results: The study included 252 women (32.5% black, 67.5% white; 56.4% pre- and early perimenopausal, 30.6% late peri- and postmenopausal, and 13.1% hormone therapy users) with a mean age of 51.2±2.6 years at baseline. In unadjusted analyses, log(PAI-1) and log(tPA-ag) were positively and significantly associated with CAC progression (p<0.05), but log(CRP) and log(fibrinogen) were not. Adjusted analyses included the following covariates: baseline CAC, age, site, race, menopausal status, income, education, systolic blood pressure, body mass index, Homeostasis Model Assessment insulin resistance index, family history of cardiovascular (CV) disease, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides, CV medication use, and current smoking. Only log(PAI-1) was significantly associated with CAC progression (OR: 1.91; 95% CI: 1.24-2.93; p=0.003). Conclusions: In conclusion, PAI-1 is associated with the presence of CAC progression in middle-aged women. Targeting PAI-1 may decrease atherogenesis beyond conventional CHD risk factors.

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.

A Specific Immunologic Assay for Functional Plasminogen Activator Inhibitor 1 in Plasma – Standardized Measurements of the Inhibitor and Related Parameters in Patients with Venous Thromboembolic Disease

1992 ◽  
Vol 68 (05) ◽  
pp. 486-494 ◽  
Author(s):  
Malou Philips ◽  
Anne-Grethe Juul ◽  
Johan Selmer ◽  
Bent Lind ◽  
Sixtus Thorsen
Keyword(s):  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Normal Subjects ◽  
Tissue Type ◽  
Blood Collection ◽  
Plasminogen Activator Inhibitor 1 ◽  
Type Plasminogen Activator ◽  
Significant Difference ◽  
Activator Inhibitor ◽  
Pai 1

SummaryA new assay for functional plasminogen activator inhibitor 1 (PAI-1) in plasma was developed. The assay is based on the quantitative conversion of PAI-1 to urokinase-type plasminogen activator (u-PA)-PAI-l complex the concentration of which is then determined by an ELISA employing monoclonal anti-PAI-1 as catching antibody and monoclonal anti-u-PA as detecting antibody. The assay exhibits high sensitivity, specificity, accuracy, and precision. The level of functional PAI-1, tissue-type plasminogen activator (t-PA) activity and t-PA-PAI-1 complex was measured in normal subjects and in patients with venous thromboembolism in a silent phase. Blood collection procedures and calibration of the respective assays were rigorously standardized. It was found that the patients had a decreased fibrinolytic capacity. This could be ascribed to high plasma levels of PAI-1. The release of t-PA during venous occlusion of an arm for 10 min expressed as the increase in t-PA + t-PA-PAI-1 complex exhibited great variation and no significant difference could be demonstrated between the patients with a thrombotic tendency and the normal subjects.

Relation between Plasminogen Activator Inhibitor-1 and Hepatic Enzyme Concentrations in Hyperlipidemic Patients

1994 ◽  
Vol 72 (03) ◽  
pp. 434-437 ◽  
Author(s):  
E Bruckert ◽  
A Ankri ◽  
P Glral ◽  
G Turpin
Keyword(s):  
Blood Pressure ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Tolerance Test ◽  
High Plasma ◽  
Oral Glucose ◽  
Plasminogen Activator Inhibitor 1 ◽  
Glutamyl Transferase ◽  
Activator Inhibitor ◽  
Pai 1

SummaryPlasminogen activator inhibitor type-1 (PAI-1) is a key determinant of the fibrinolytic capacity. Its activity correlates with most of the characteristic features of insulin resistance syndrome, i. e. obesity, high blood pressure and hyperlipidemia.We measured plasma PAI-1 antigen levels in 131 asymptomatic men (aged 44.2 ± 11 years) who had been referred for hyperlipidemia. Those taking medication and those with a secondary hyperlipidemia were excluded.We confirmed the correlation between PAI-1 levels and the following variables: body mass index, blood pressure, triglyceride concentration, and blood glucose and insulin levels before and after an oral glucose tolerance test. We also found a significant and independent correlation between PAI-1 and the concentration of the hepatic enzymes glutamyl transferase, alanine aminotransferase and aspartate aminotransferase.Mild liver abnormalities (presumably steatosis) may thus be one of the factors accounting for high plasma PAI-1 levels in hyperlipidemic patients.

The Roles of α2-Antiplasmin and Plasminogen Activator Inhibitor 1 (PAI-1) in the Inhibition of Clot Lysis

1993 ◽  
Vol 70 (02) ◽  
pp. 301-306 ◽  
Author(s):  
Linda A Robbie ◽  
Nuala A Booth ◽  
Alison M Croll ◽  
Bruce Bennett
Keyword(s):  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Fibrin Clot ◽  
Clot Lysis ◽  
Plasminogen Activator Inhibitor 1 ◽  
Dependent Inhibition ◽  
Activator Inhibitor ◽  
Pai 1

SummaryThe relative importance of the two major inhibitors of fibrinolysis, α2-antiplasmin (α2-AP) and plasminogen activator inhibitor (PAI-1), were investigated using a simple microtitre plate system to study fibrin clot lysis in vitro. Cross-linked fibrin clots contained plasminogen and tissue plasminogen activator (t-PA) at concentrations close to physiological. Purified α2-AP and PAI-1 caused dose-dependent inhibition. All the inhibition due to normal plasma, either platelet-rich or poor, was neutralised only by antibodies to α2-AP. Isolated platelets, at a final concentration similar to that in blood, 2.5 × 108/ml, markedly inhibited clot lysis. This inhibition was neutralised only by antibodies to PAI-1. At the normal circulating ratio of plasma to platelets, α2-AP was the dominant inhibitor. When the platelet:plasma ratio was raised some 20-fold, platelet PAI-1 provided a significant contribution. High local concentrations of PAI-1 do occur in thrombi in vivo, indicating a role for PAI-1, complementary to that of α2-AP, in such situations.

Determinants of Plasminogen Activator Inhibitor-1 Activity in Survivors of Myocardial Infarction

1995 ◽  
Vol 73 (02) ◽  
pp. 261-267 ◽  
Author(s):  
Rosaire P Gray ◽  
Vidya Mohamed-Ali ◽  
David L H Patterson ◽  
John S Yudkin
Keyword(s):  
Myocardial Infarction ◽  
Plasminogen Activator ◽  
Plasma Insulin ◽  
Plasminogen Activator Inhibitor ◽  
Immunoreactive Insulin ◽  
Plasminogen Activator Inhibitor 1 ◽  
Serum Triglycerides ◽  
Fasting Plasma ◽  
Activator Inhibitor ◽  
Pai 1

SummaryA significant relationship has been described between plasminogen activator inhibitor-1 (PAI-1) and plasma insulin concentrations. However, most radioimmunoassays (RIA) substantially overestimate plasma insulin concentrations because of cross reaction with proinsulin-like molecules and it has been proposed that proinsulin-like molecules may be important determinants of PAI-1 activity. We measured fasting plasma immunoreactive insulin by conventional RIA, fasting plasma insulin (EIMA) by specific two site immuno-enzymometric assay, and intact proinsulin and des-31,32-proinsulin by two site immunoradiometric assay (IRMA) in 74 (50 nondiabetic and 24 diabetic) subjects who had survived a myocardial infarction between 6 and 24 months previously. In univariate analysis, PAI-1 activity correlated with serum triglycerides (rs=0.43; p <0.0001), insulin sensitivity (rs = -0.30; p = 0.004), and immunoreactive insulin (rs = 0.45; p <0.0001). However, the relationship between PAI-1 activity and plasma specific insulin (IEMA) was weaker (rs = 0.24; p = 0.019) than those with intact proinsulin (rs = 0.53; p <0.0001) and des-31,32-proinsulin (rs = 0.54; p <0.0001) despite the low concentrations of these proinsulin-like molecules. In multiple regression analysis, only des-31,32-proinsulin (p = 0.001) and serum triglycerides (p = 0.013) were significant determinants of PAI-1 activity. In conclusion, these results suggest that proinsulin-like molecules and serum triglycerides are important determinants of PAI-1 activity in survivors of myocardial infarction.

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