scholarly journals The Association of the Metabolic Syndrome with PAI-1 and t-PA Levels

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Christopher S. Coffey ◽  
Folkert W. Asselbergs ◽  
Patricia R. Hebert ◽  
Hans L. Hillege ◽  
Qing Li ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Plasminogen Activator ◽  
Smoking Status ◽  
Plasminogen Activator Inhibitor ◽  
Population Based ◽  
The Metabolic Syndrome ◽  
And Gender ◽  
Activator Inhibitor Type ◽  
End Stage ◽  
Pai 1

Background. We used a random sample (n=2,495) from the population-based Prevention of Renal and Vascular End-stage Disease (PREVEND) study population to examine the association of the metabolic syndrome (Met S) with plasminogen activator inhibitor type 1 (PAI-1) and tissue plasminogen activator (t-PA) antigen levels.Results. The overall prevalence of the Met S was 18%, was dependent on age and gender, and was positively associated with higher antigen levels of both PAI-1 and t-PA. These significant effects were maintained after adjustment for age, gender, BMI, elevated C-reactive protein, smoking status, urinary albumin excretion, and insulin levels. We found no significant interactions between the Met S and other covariates on PAI-1 and t-PA levels.Conclusions. Our study demonstrates that those with the Met S have significantly higher levels of PAI-1 and t-PA antigen, factors known to increase the risk of cardiovascular disease.

Regulation of plasminogen activator inhibitor type 1 gene expression by inflammatory mediators and statins

2008 ◽  
Vol 100 (12) ◽  
pp. 969-975 ◽  
Author(s):  
Egbert K. O. Kruithof
Keyword(s):  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
The Metabolic Syndrome ◽  
Plasminogen Activator Inhibitor Type ◽  
Inflammatory Stimuli ◽  
Inhibitor Type ◽  
Activator Inhibitor Type ◽  
Activator Inhibitor ◽  
Pai 1

SummaryElevated plasma concentrations of plasminogen activator inhibitor type 1 (PAI-1), also named serpin E1, are encountered in patients with thrombophilia, atherosclerosis, septicemia and the metabolic syndrome and may be associated with an increased risk of complications. Expression of PAI-1 is increased by inflammatory stimuli and decreased by statins, drugs widely used in patients with cardiovascular disease. Increased expression of PAI-1 by inflammatory stimuli is mediated by a large variety of signal transduction pathways, which include the NF-κB and MAP kinase pathways. The downregulating effect of statins on PAI-1 expression is dependent on the inhibition of Rho family proteins and may involve an activation of PI-3 kinase/Akt signaling pathways. In this review we summarize the findings on the effect of inflammation and statins on PAI-1 expression.

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>

Demonstration of three distinct high molecular weight complexes between plasminogen activator inhibitor type 1 and tissue type plasminogen activator.

2021 ◽  
Author(s):  
Tae Ito ◽  
Yuko Suzuki ◽  
Hideto Sano ◽  
Naoki Honkura ◽  
Francis J Castellino ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Type Plasminogen Activator ◽  
Sds Page ◽  
Inhibitor Type ◽  
Activator Inhibitor Type ◽  
Pai 1

Background: Details of the molecular interaction between tissue type plasminogen activator (tPA) and plasminogen activator inhibitor type-1 (PAI-1) remain unknown. Methods and Results: Three distinct forms of high molecular weight complexes are demonstrated. Two of the forms were detected by mass spectrometry. The high molecular mass detected by MALDI-TOF MS spectrometry was 107,029 Da, which corresponds to the sum of molecular masses of the intact tPA (65,320 Da) and the intact PAI-1 (42,416 Da). The lower molecular mass was 104,367 Da and is proposed to lack the C-terminal bait peptide of PAI-1 (calculated mass, 3,804 Da) which was detected as a 3,808 Da fragment. When the complex was analyzed by SDS-PAGE, only a single band was observed. However, after treatment by SDS and Triton X-100, two distinct forms of the complex with different mobilities were shown by SDS-PAGE. The higher molecular weight band demonstrated specific tPA activity on fibrin autography, whereas the lower molecular weight band did not. Peptide sequence analysis of these two bands, however, unexpectedly revealed the existence of the C-terminal cleavage peptide in both bands and its amount was less in the upper band. In the upper band, the sequences corresponding to the regions at the interface between two molecules in its Michaelis intermediate were diminished. Thus, these two bands corresponded to distinct nonacyl-enzyme complexes, wherein only the upper band liberated free tPA under the conditions employed. Conclusion: These data suggest that under physiological conditions a fraction of the tPA-PAI-1 population exists as non-acylated-enzyme inhibitor complex.

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.

Lipoprotein (a) up-regulates the expression of the plasminogen activator inhibitor 2 in human blood monocytes

Blood ◽  
2001 ◽  
Vol 97 (4) ◽  
pp. 981-986 ◽  
Author(s):  
Christa Buechler ◽  
Heidrun Ullrich ◽  
Mirko Ritter ◽  
Mustafa Porsch-Oezcueruemez ◽  
Karl J. Lackner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Blood Monocytes ◽  
Plasminogen Activator Inhibitor Type ◽  
Inhibitor Type ◽  
Activator Inhibitor Type ◽  
Gender Specific ◽  
Activator Inhibitor ◽  
Pai 1

Abstract Elevated plasma lipoprotein (a) (Lp[a]) and cardiac events show a modest but significant association in various clinical studies. However, the influence of high Lp(a) on the gene expression in blood monocytes as a major cell involved in atherogenesis is poorly described. To identify genes influenced by elevated serum Lp(a), the gene expression was analyzed on a complementary DNA microarray comparing monocytes from a patient with isolated Lp(a) hyperlipidemia and coronary heart disease with monocytes from a healthy blood donor with low Lp(a). By using this approach, numerous genes were found differentially expressed in patient-versus-control monocytes. Verification of these candidates by Northern blot analysis or semiquantitative polymerase chain reaction in monocytes from additional patients with Lp(a) hyperlipidemia and healthy blood donors with elevated Lp(a) confirmed a significant induction of plasminogen activator inhibitor type 2 (PAI-2) messenger RNA (mRNA) in monocytes from male, but not from female, individuals with high Lp(a), indicating that this observation is gender specific. This led also to increased intracellular and secreted PAI-2 protein in monocytes from male probands with Lp(a) hyperlipidemia. Plasminogen activator inhibitor type 1 (PAI-1) mRNA was found suppressed only in the patients′ monocytes and not in healthy probands with high Lp(a) levels. Purified Lp(a) induced PAI-2 mRNA and protein and reduced PAI-1 expression in monocytes isolated from various controls. The finding that PAI-2 is elevated in monocytes from male patients with isolated Lp(a) hyperlipidemia and male healthy probands with high Lp(a) and that purified Lp(a) up-regulates PAI-2 in control monocytes in vitro indicate a direct, but gender-specific, effect of Lp(a) for the induction of PAI-2 expression.

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