High PAI activity with correlation to triglyceride and HDL cholesterol values in patients with coronary artery disease with no difference in survivors of myocardial infarction

Abstract

The fibrinolytic capacity of blood depends mainly on the amount of tissue-type plasminogen activator (t-PA) activity and plasminogen activator inhibitor type-1 (PAI-1) activity. Previous studies linked high PAI activity or low t-PA activity with the development of atherosclerosis and thromboembolic diseases. Yet, there are conflicting reports in the literature as to whether there is higher PAI activity in patients with myocardial infarction (MI) than in patients with coronary artery disease (CAD) without previous MI. In this retrospective study, t-PA activity, t-PA antigen, and PAI activity before and after a venous occlusion test (VOT) of 10 min were assessed in 109 patients with angiographically documented CAD, in two subgroups of CAD patients with (n = 66) or without (n = 43) previous MI, and in subgroups of CAD patients according to their triglyceride levels and other risk factors. The mean values of t-PA activity in the whole patient group showed a 100-fold increase and a 3.1-fold increase in t-PA antigen after VOT (0.03 +/- 0.03 to 3.0 +/- 6.8 U/ml and 16.5 +/- 6.9 to 51.0 +/- 25.4 ng/ml, p < 0.05). PAI activity was 24.4 +/- 11.0 before and 19.6 +/- 13.2 U/ml after VOT. Within the CAD group, no difference was found between patients without MI and survivors of previous MI in PAI activity before VOT (24.6 +/- 10.7 vs. 24.3 +/- 11.3 U/ml) and after VOT (19.0 +/- 12.1 vs 20.0 +/- 14.0 U/ml), or t-PA activity before (0.03 +/- 0.01 vs. 0.04 +/- 0.04 U/ml) and after VOT (2.8 +/- 7.0 vs. 3.2 +/- 6.7 U/ml). In 39.4% of CAD patients elevated plasma PAI activity before VOT (> 25 U/ml) was found. This subgroup of patients represented the highest PAI activity after VOT (p < 0.05), the lowest t-PA activity after VOT (p < 0.001), and the highest triglyceride levels (p < 0.05). In 11% of the patients, a small increase in t-PA activity (less than 0.5 U/ml) after VOT was seen. This group showed the lowest t-PA antigen after VOT (p < 0.001) and the highest fibrinogen level (p < 0.05). Both subgroups showed the same distribution among patients with and without MI. CAD patients with triglyceride levels over 200 mg/dl had the highest PAI activity values before VOT (28.3 +/- 11.8 U/ml; p < 0.01) and after VOT (24.9 +/- 13.2 U/ml; p < 0.01), resulting in low t-PA activity after VOT (p < 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Phosphorothioate Oligodeoxyribonucleotides Antisense to PAI-1 mRNA Increase Fibrinolysis and Modify Experimental Thrombosis in Rats

“…The efficacy of PAI-1 in preventing thrombolysis was recently tested in animal models. The reactivated PAI-1 could rapidly reverse the bleeding tendency induced by the combination of rt-PA and aspirin in rabbits (31) and effectively prevented thrombolysis in vivo (32). Hence, it was suggested that PAI-1 may be used as an antidote to treat hemorrhagic complications brought about by the administration of thrombolytic agents (32).…”

“…The reactivated PAI-1 could rapidly reverse the bleeding tendency induced by the combination of rt-PA and aspirin in rabbits (31) and effectively prevented thrombolysis in vivo (32). Hence, it was suggested that PAI-1 may be used as an antidote to treat hemorrhagic complications brought about by the administration of thrombolytic agents (32). On the other hand, neutralization of plasma PAI-1 by monoclonal antibody (13) or low molecular weight inhibitors (14) increased fibrinolysis and protected against thrombus formation in animals.…”

Blockade of the neuropeptide Y Y2 receptor with the potent antagonist BIIE0246 regulates gene expression levels in the lipid metabolic pathways in human hepatoma cell line HepG2

“…PLG is plasminogen and closely linked to tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) in this pathway. In the previous report, PAI-1 is negatively correlated with plasma HDL-cholesterol levels [25]. Thus plasminogen up-regulation may lead to higher plasma levels of HDL-cholesterol.…”