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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:1378-1386.)
© 1999 American Heart Association, Inc.

Brief Reviews

Plasminogen Activator Inhibitor Type 1 in Ischemic Cardiomyopathy

Maurizio Cesari; Gian Paolo Rossi

From the Department of Clinical and Experimental Medicine, University of Padua Medical School, Padua, Italy.

Correspondence to G.P. Rossi, MD, FACC, Clinica Medica 4, Department of Clinical and Experimental Medicine, University Hospital, Via Giustiniani, 2, 35126 Padova, Italy. E-mail gprossi@ux1.unipd.it

Key Words: plasminogen activator inhibitor • myocardial infarction • coronary artery disease • gene polymorphism

	Introduction

 
Plasminogen activator inhibitor type 1 (PAI-1) is a proteinase inhibitor¹ constituting the key regulator² of the activity of the fibrinolytic system, an important protective mechanism against thrombosis. Because a reduced fibrinolytic activity, mainly caused by increased plasma levels of PAI-1, was a common finding in cross-sectional studies of patients with coronary artery disease (CAD),³ high PAI-1 levels have been regarded as a risk factor for recurrent myocardial infarction (MI).^{4 5 6} It has also been proposed that a reduced fibrinolytic activity may have a role in atherosclerotic plaque formation and in a prothrombotic state, carrying an increased risk of arterial occlusion. Accordingly, over the last few years, several studies have been performed to investigate the role of plasma PAI-1 levels in the development of CAD and MI. Moreover, the observation that polymorphisms of the PAI-1 gene exist, some of which apparently associated with increased plasma PAI-1 levels, stimulated studies aiming at investigating the potential relation between PAI-1 genotypes and ischemic cardiomyopathy.

Thus, we shall focus on recent advances in the knowledge of the role of PAI-1 and its gene in the development of ischemic cardiomyopathy.

	Biochemical Features

 
Intravascular fibrinolytic activity results from a balance between plasminogen activators, such as the tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA), and inhibitors, such as PAI-1 and 2-antiplasmin. PAI-1 is a glycoprotein with a molecular mass of 54 kDa that belongs to the serine protease inhibitor superfamily (serpins). Its primary structure was deduced from the sequence of its cDNA.⁷ It is considered the major physiological inhibitor . . . [Full Text of this Article]

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