Plasminogen Activator Inhibitor-1 (PAI-1) Antigen Plasma Levels in Subjects Attending a Metabolic Ward: Relation to Polymorphisms of PAI-1 and Angiontensin Converting Enzyme (ACE) Genes

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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Role of 4G/5G plasminogen activator inhibitor-1 (PAI-1) gene polymorphism and the PAI-1 plasma levels in the outcome of patients with severe sepsis

Critical Care ◽

10.1186/cc7516 ◽

2009 ◽

Vol 13 (Suppl 1) ◽

pp. P352 ◽

Cited By ~ 2

Author(s):

L Lorente ◽

M Martín ◽

L Labarta ◽

C Díaz ◽

J Solé-Violán ◽

...

Keyword(s):

Severe Sepsis ◽

Gene Polymorphism ◽

Plasminogen Activator ◽

Plasma Levels ◽

Plasminogen Activator Inhibitor ◽

Plasminogen Activator Inhibitor 1 ◽

Activator Inhibitor ◽

Pai 1

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The plasminogen activator inhibitor-1 (pai-1) gene locus 4g/5g polymorphism and Pai-1 plasma levels in Egyptian patients with myocardial infarction

Egyptian Journal of Biochemistry and Molecular Biology ◽

10.4314/ejbmb.v29i1.67383 ◽

2011 ◽

Vol 29 (1) ◽

Author(s):

MA Al Tahhan ◽

RL Etewa ◽

AEA Gomaa

Keyword(s):

Myocardial Infarction ◽

Plasminogen Activator ◽

Plasma Levels ◽

Gene Locus ◽

Plasminogen Activator Inhibitor ◽

Plasminogen Activator Inhibitor 1 ◽

Egyptian Patients ◽

Activator Inhibitor ◽

Pai 1

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High plasma levels of plasminogen activator inhibitor 1 (PAI-1) in polycythemia vera and essential thrombocythemia are associated with thrombosis

Thrombosis Research ◽

10.1016/0049-3848(94)90226-7 ◽

1994 ◽

Vol 75 (5) ◽

pp. 513-520 ◽

Cited By ~ 17

Author(s):

JoséA. Cancelas ◽

Angel García-Avello ◽

Luis J. García-Frade

Keyword(s):

Polycythemia Vera ◽

Plasminogen Activator ◽

Essential Thrombocythemia ◽

Plasma Levels ◽

Plasminogen Activator Inhibitor ◽

High Plasma ◽

Plasminogen Activator Inhibitor 1 ◽

Activator Inhibitor ◽

Pai 1

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A Decrease in Plasminogen Activator Inhibitor-1 Activity after Successful Percutaneous Transluminal Coronary Angioplasty Is Associated with a Significantly Reduced Risk for Coronary Restenosis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648414 ◽

1992 ◽

Vol 67 (02) ◽

pp. 209-213 ◽

Cited By ~ 54

Author(s):

Kurt Huber ◽

Maria Jörg ◽

Peter Probst ◽

Ernst Schuster ◽

Irene Lang ◽

...

Keyword(s):

Plasminogen Activator ◽

Coronary Angioplasty ◽

Plasma Levels ◽

Plasminogen Activator Inhibitor ◽

Plasminogen Activator Inhibitor 1 ◽

Coronary Restenosis ◽

Group A ◽

Activator Inhibitor ◽

Pai 1 ◽

Observation Period

SummaryTo determine a possible relation of changes in plasma levels of plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (t-PA) to the development of coronary restenosis after successful coronary angioplasty (PTC A), we followed 104 patients with a low grade residual stenosis after PTCA (less than 30%) for a period of 12 months. PAI-1 plasma levels (functional activity) and t-PA antigen were determined 1 day before PTCA and 3 days, 3 months and 6 months thereafter. Thirty-four patients (32.69%) developed angiographically proven coronary restenosis (group A) within a time range of 4-48 weeks (median 12.5 weeks) after PTCA while the remaining patients (group B) had neither clinical signs nor angiographic evidence of restenosis after 6 months. No significant differences could be demonstrated in t-PA antigen or PAI-1 activity (plasma levels between the two groups of patients the day before PTCA). During the whole observation period t-PA plasma levels were not significantly different between the two groups; however, PAI-1 plasma levels were significantly higher at 3 months and 6 months after PTCA in patients of group A (p <0.005). When the pattern of PAI-1 plasma levels over time (increase or decrease between two consecutive time points of blood collection) was used to discriminate between the two study groups only 3.5-18% of patients with a decrease in PAI-1 developed coronary restenosis within the following observation period in contrast to 25-58% of patients with an increase in PAI-1 plasma levels (p <0.05 to p <0.0005).

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

Thrombosis and Haemostasis ◽

10.1160/th03-03-0159 ◽

2003 ◽

Vol 90 (10) ◽

pp. 717-723 ◽

Cited By ~ 1

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.

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Plasminogen Activator Inhibitor-1 (PAI-1) 4G/5G Polymorphism, Coronary Thrombosis, and Myocardial Infarction in Middle-aged Finnish Men who Died Suddenly

Thrombosis and Haemostasis ◽

10.1055/s-0037-1613971 ◽

2000 ◽

Vol 84 (07) ◽

pp. 78-82 ◽

Cited By ~ 20

Author(s):

Markus Perola ◽

Ulla Wartiovaara ◽

Leena Peltonen ◽

Aarno Palotie ◽

Antti Penttilä ◽

...

Keyword(s):

Myocardial Infarction ◽

Plasminogen Activator ◽

Plasma Levels ◽

Coronary Thrombosis ◽

Plasminogen Activator Inhibitor ◽

Hospital Death ◽

Middle Aged ◽

Plasminogen Activator Inhibitor 1 ◽

Activator Inhibitor ◽

Pai 1

SummaryHigh plasminogen activator inhibitor-1 (PAI-1) plasma levels increase future risk of myocardial infarction (MI). The 4G allele of the 4G/5G polymorphism of the PAI-1 gene has been associated with increased plasma levels of PAI-1. The association of the PAI-1 polymorphism with coronary narrowings, coronary thrombosis and myocardial infarction (MI) was studied in a prospective autopsy series of 300 middle-aged Caucasian Finnish men (33 to 69 yrs) suffering sudden out-of-hospital death (Helsinki Sudden Death Study). The 4G allele was found in 76.8% of men with sudden cardiac death (SCD) compared to 67.5% in men who died accidentally and 63.2% in men who died of other diseases (p = 0.08 and p = 0.055, respectively). Men possessing the 4G allele had more often acute MI (OR 3.5; p <0.05) and coronary thrombosis (OR 5.5; p = 0.01) compared to 5G homozygotes. 5G homozygotes, comprising one third of the men in our study, seem to be at a decreased risk of thrombosis, whereas carriers of the common 4G allele have an increased risk of thrombosis, AMI and possibly SCD compared to 5G homozygotes.

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