Hypertension and hemostatic/fibrinolytic balance disorders

Background: Hypertension is one of the principal risk factors for cardiovascular disease. We aimed to evaluate the impact of hypertension on fibrinolytic balance and endothelial function by measuring plasma levels of plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator antigen (tPA), tPA/PAI-1 complex and fibrinogen. Methods: Patients enrolled into the study were divided into four groups: 22 essential hypertensive (EH), 22 white coat hypertensive (WCH), 22 renovascular hypertensive (RH) and 22 normotensive control subjects. Plasma PAI-1, tPA, tPA/PAI-1 complex levels were measured by enzyme linked immunosorbent assays. Results: There was no difference in the systolic and diastolic blood pressure measurements of the EH and RH groups. The four groups were comparable for age, gender, smoking habits and BMI. Patients with EH, RH and WCH had increased plasma levels of PAI-1, tPA, tPA/PAI-1 complex and fibrinogen compared with controls. No fibrinolytic parameter was associated with blood pressure in hypretensive subjects. Conclusion: This prospective study showed that fibrinolytic markers such as PAI-1, tPA, tPA/PAI-1 complex are independently associated with the development of hypertension. This supports the hypothesis that disturbances in fibrinolysis precede a cardiovascular event. Therefore, hypertension may be associated with impaired fibrinolysis.

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

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648885 ◽

1994 ◽

Vol 72 (03) ◽

pp. 434-437 ◽

Cited By ~ 10

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.

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The mechanism of the reaction between human plasminogen-activator inhibitor 1 and tissue plasminogen activator

Biochemical Journal ◽

10.1042/bj2650109 ◽

1990 ◽

Vol 265 (1) ◽

pp. 109-113 ◽

Cited By ~ 74

Author(s):

T L Lindahl ◽

P I Ohlsson ◽

B Wiman

Keyword(s):

Amino Acid ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Plasminogen Activator Inhibitor ◽

Peptide Bond ◽

Plasminogen Activator Inhibitor 1 ◽

Sds Page ◽

Tissue Plasminogen ◽

Activator Inhibitor ◽

Pai 1

The structural events taking place during the reaction between PAI-1 (plasminogen-activator inhibitor 1) and the plasminogen activators sc-tPA (single-chain tissue plasminogen activator) and tc-tPA (two-chain tissue plasminogen activator) were studied. Complexes were formed by mixing sc-tPA or tc-tPA with PAI-1 in slight excess (on an activity basis). The complexes were purified from excess PAI-1 by affinity chromatography on fibrin-Sepharose. Examination of the purified complexes by SDS/polyacrylamide-gel electrophoresis (SDS/PAGE) and N-terminal amino acid sequence analysis demonstrated that a stoichiometric 1:1 complex is formed between PAI-1 and both forms of tPA. Data obtained from both complexes revealed the amino acid sequences of the parent molecules and, in addition, a new sequence: Met-Ala-Pro-Glu-Glu-. This sequence is found in the C-terminal portion of the intact PAI-1 molecule and thus locates the reactive centre of PAI-1 to Arg346-Met347. The proteolytic activity of sc-tPA is demonstrated by its capacity to cleave the ‘bait’ peptide bond in PAI-1. The complexes were inactive and dissociated slowly at physiological pH and ionic strength, but rapidly in aq. NH3 (0.1 mol/l). Amidolytic tPA activity was generated on dissociation of the complexes, corresponding to 0.4 mol of tPA/mol of complex. SDS/PAGE of the dissociated complexes indicated a small decrease in the molecular mass of PAI-1, in agreement with proteolytic cleavage of the ‘bait’ peptide bond during complex-formation.

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Plasminogen activator inhibitor-1 4G/5G promoter polymorphism and PAI-1 plasma levels in young patients with ischemic stroke

Molecular Biology Reports ◽

10.1007/s11033-011-0687-4 ◽

2011 ◽

Vol 38 (8) ◽

pp. 5355-5360 ◽

Cited By ~ 16

Author(s):

Adriano de Paula Sabino ◽

Daniel Dias Ribeiro ◽

Caroline Pereira Domingueti ◽

Mariana Silva dos Santos ◽

Telma Gadelha ◽

...

Keyword(s):

Ischemic Stroke ◽

Plasminogen Activator ◽

Plasma Levels ◽

Young Patients ◽

Plasminogen Activator Inhibitor ◽

Promoter Polymorphism ◽

Plasminogen Activator Inhibitor 1 ◽

Activator Inhibitor ◽

Pai 1

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W1490: Association Between Plasma Levels of Plasminogen Activator Inhibitor-1 (PAI-1) and Colorectal Adenomas

Gastrointestinal Endoscopy ◽

10.1016/j.gie.2010.03.902 ◽

2010 ◽

Vol 71 (5) ◽

pp. AB341

Author(s):

Eun Ran Kim ◽

Moon Hee Yang ◽

Yeun Jung Lim ◽

Jin Hee Lee ◽

Byung-Hoon Min ◽

...

Keyword(s):

Plasminogen Activator ◽

Plasma Levels ◽

Plasminogen Activator Inhibitor ◽

Colorectal Adenomas ◽

Plasminogen Activator Inhibitor 1 ◽

Activator Inhibitor ◽

Pai 1

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Impact of statin therapy on plasma levels of plasminogen activator inhibitor-1

Thrombosis and Haemostasis ◽

10.1160/th15-10-0770 ◽

2016 ◽

Vol 116 (07) ◽

pp. 162-171 ◽

Cited By ~ 14

Author(s):

Amirhossein Sahebkar ◽

Cristiana Catena ◽

Kausik Ray ◽

Antonio Vallejo-Vaz ◽

Željko Reiner ◽

...

Keyword(s):

Statin Therapy ◽

Plasminogen Activator ◽

Publication Bias ◽

Plasma Levels ◽

Meta Analysis ◽

Plasminogen Activator Inhibitor ◽

Lipid Lowering ◽

Plasminogen Activator Inhibitor 1 ◽

Activator Inhibitor ◽

Pai 1

SummaryElevated plasma levels of the pro-thrombotic and pro-inflammatory factor plasminogen activator inhibitor-1 (PAI-1) may contribute to the pathogenesis of atherosclerotic cardiovascular disease. Beyond their lipid-lowering effect, statins have been shown to modulate plasma PAI-1 levels but evidence from individual randomised controlled trials (RCTs) is controversial. Therefore, we aimed to assess the potential effects of statin therapy on plasma PAI-1 concentration through a meta-analysis of RCTs. We searched Medline and SCOPUS databases (up to October 3, 2014) to identify RCTs investigating the effect of statin therapy on plasma PAI-1 concentrations. We performed random-effects meta-analysis and assessed heterogeneity (I2 test, subgroup and sensitivity analyses) and publication bias (funnel plot, Egger and “trim and fill” tests). Sixteen RCTs (comprising 19 treatment arms) were included and pooled analyses showed a significant effect of statins in reducing plasma PAI-1 concentrations (weighted mean difference WMD: –15.72 ng/ml, 95 % confidence interval [CI]: –25.01, –6.43,). In subgroup analysis, this effect remained significant in with lipophilic statins (atorvastatin and simvastatin) (WMD: –21.32 ng/ml, 95 % CI: –32.73, –9.91, I2=99 %) and particularly atorvastatin (WMD: –20.88 ng/mL, 95 % CI: –28.79, –12.97, I2=97 %). In the meta-regression analysis, the impact of statins on PAI-1 did not correlate with the administered dose, duration of treatment and changes in plasma LDL-cholesterol concentrations. Finally, evidence of publication bias was observed. In conclusion, taking into account the limit of heterogeneity between studies, the present meta-analysis suggests that statin therapy (mainly atorvastatin) significantly lowers plasma PAI-1 concentrations.

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