Plasminogen Activator Inhibitor-1 Promoter 4G/5G Genotype and Plasma Levels in Relation to a History of Myocardial Infarction in Patients Characterized by Coronary Angiography

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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Relationship of Plasminogen Activator Inhibitor-1 Levels following Thrombolytic Therapy with rt-PA as Compared to Streptokinase and Patency of Infarct Related Coronary Artery

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614637 ◽

1999 ◽

Vol 82 (07) ◽

pp. 104-108 ◽

Cited By ~ 13

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.

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

Thrombosis and Haemostasis ◽

10.1055/s-0038-1653762 ◽

1995 ◽

Vol 73 (02) ◽

pp. 261-267 ◽

Cited By ~ 19

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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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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Relationship among HbA1c and Some Markers of Endothelial Damage in Type 2 Diabetes Mellitus

International Blood Research & Reviews ◽

10.9734/ibrr/2019/v9i230097 ◽

2019 ◽

pp. 1-6

Author(s):

Ifeanyichukwu Martin Ositadinma ◽

Ngwu Amauche Martina ◽

Eluke Blessing Chekwube

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Plasminogen Activator ◽

Plasma Levels ◽

Plasminogen Activator Inhibitor ◽

Diabetic Patients ◽

Plasminogen Activator Inhibitor 1 ◽

Activator Inhibitor

Background: A number of processes regulating the thrombolytic balance are impaired in diabetic patients as a result of dysfunction of endothelial cells leading to a hypercoagulative state. Von Willebrand factor (VWF) is an important marker of endothelial dysfunction. Plasminogen activator inhibitor-1 antigen (PAI-1-Ag), the major physiological inhibitor of tissue plasminogen activator (tPA), is mainly produced by endothelium. The aim of this study is to measure plasma levels of von Willebrand factor, Plasminogen activator inhibitor-1 antigen in type 2 diabetes mellitus patients and to correlate with glycated haemoglobin (HbA1c). Study Design: This prospective cohort study was conducted on 30 diagnosed type 2 DM patients who were about to start treatment. Place and Duration of Study: Medical outpatient (MOP) clinic of Enugu State University of Science and Technology Teaching Hospital (ESUTTH), between January and December 2016. Methodology: We included 30 patients (13 men, 17 women; age range 40-80 years) with type 2 diabetes mellitus. Blood samples were drawn from the patients before they commenced treatment, six months into the treatment and at twelve months of the treatment. Blood samples were also drawn from 25 age matched non diabetic patients. Plasma von Willebrand factor and Plasminogen activator inhibitor-1 antigen levels were determined by Enzyme linked immunosorbent assay. Glycated haemoglobin (HbA1c) and fasting blood sugar (FBS) levels were also evaluated along with them. Results: This study was conducted on 30 type 2 DM patients consisting of 13 males and 17 females. At treatment naïve, mean levels of vWF were significantly increased (45.48 +/- 6.46) in male type 2 Diabetic patients compared to the control (20.45 +/- 0.26). Six months into treatment mean levels of vWF were significantly increased (48.18 +/- 4.99) in female type 2 Diabetic patients compared to the control (37.64 +/- 7.93). The plasma levels of vWF were significantly and positively correlated with HbA1c at six months into treatment in male type 2 DM patients. The plasma levels of vWF were also significantly and positively correlated with PAI-1 at six and twelve months into treatment in both genders. Conclusion: There was strong significant positive correlation between plasma levels of vWF and PAI-1 in type 2 diabetes mellitus patients.

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