Impaired fibrinolysis in angiographically documented coronary artery disease.

Adriano Basques Fernandes,Marinez Oliveira Sousa,Bashir Abdulgader Lwaleed,Luciana Moreira Lima,Rashid Saeed Kazmi,Maria Das Graças Carvalho,Vicente De Paulo Coelho Toledo

doi:10.1155/2015/214680

Abstract

Impaired fibrinolysis may predispose to coronary artery disease (CAD). Hypofibrinolysis due to high levels of plasminogen activator inhibitor-1 (PAI-1) has been reported in CAD. A novel regulator of fibrinolytic activity, thrombin activatable fibrinolysis inhibitor (TAFI), has attracted attention in recent years. It acts by blocking the formation of a ternary complex of plasminogen, fibrin, and tissue plasminogen activator (t-PA). Previously ambiguous results regarding TAFI levels have been reported in CAD. We measured plasma levels of PAI-1 and TAFI antigen in 123 patients with age ranging from 40 to 65 years who had been submitted to coronary angiography and assessed the association of these markers with the extent of stenosis in three groups: angiographically normal artery (NAn), mild to moderate atheromatosis (MA), and severe atheromatosis (SA). Plasma levels of PAI-1 were increased in patients with severe atheromatosis compared to mild/moderate atheromatosis or to normal patients (66.60, 40.50, and 34.90 ng/mL, resp.; P < 0.001). For TAFI no difference was found between different groups. When patients were grouped in only two groups based on clinical cut-off point for intervention (stenosis less than or above 70%) we found increased plasma levels for PAI-1 (37.55 and 66.60 ng/mL, resp.; P < 0.001) and decreased plasma levels for TAFI (5.20 and 4.53 μg/mL, resp.; P = 0.04) in patients with stenosis above 70%. No difference was found in PAI-1 or TAFI levels comparing the number of affected vessels. Conclusion. As evidenced by a raised level of PAI-1 antigen, one can suggest an impaired fibrinolysis in stable CAD, although no correlation with the number of affected vessels was found. Curiously, a decreased plasma level of total TAFI levels was observed in patients with stenosis above 70%. Further studies measuring functional TAFI are required in order to elucidate its association with the extent of degree of atheromatosis.

Highlights

The endothelium mediates a variety of vital physiological functions
We explored the severity of coronary artery disease (CAD) through the number of affected vessels in patients with stenosis of more than 70% versus plasma levels of plasminogen activator inhibitor-1 (PAI-1) and thrombin activatable fibrinolysis inhibitor (TAFI)
Maintaining a balance between thrombin-stimulated fibrin clot formation and plasmininduced clot lysis is essential for optimal haemostasis

Summary

Introduction

The endothelium mediates a variety of vital physiological functions. While in health it maintains vascular integrity by expressing vasoprotective and thromboresistant molecules, on activation endothelial cells (ECs) acquire a phenotype that promotes atherosclerosis [1]. The formation of thrombus is followed by the process of fibrinolysis which consists of an enzymatic dissolution of the fibrin clot by plasmin. It is controlled by endothelial cells through secretion of physiological plasminogen activators like tissue type plasminogen activator (t-PA) and urokinase type plasminogen activator (u-PA). Plasmin is generated on the surface of endothelial cells in the presence or absence of fibrin. The endothelium exerts an inhibitory effect on fibrinolysis through the synthesis of an inhibitor, type 1 plasminogen

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