PAI -1 INHIBITOR AS BIOMARKER OF CARDIORENAL DAMAGE

Abstract

Plasminogen activator inhibitor 1 (PAI-1), which belongs to the family of serine protease inhibitors  is the primary regulator of plasminogen activity. PAI-1 is synthesized as a single-chain glycopeptide and is deposited in the platelets in a latent form, from which it is released upon their activation. It is spontaneously converted into stable molecules, unless it reacts with proteins from the plasma. As a powerful inhibitor of fibrinolysis, it participates in the pathogenesis of endothelial damage, processes of accelerated atherosclerosis and thromboembolism. All the diseases of the cardiovascular system which are dominated by the processes of fibrosis and thrombosis lead to an increase in PAI-1 in the circulation. In the emergence and development of atherosclerosis, it plays a role not only in the formation of intraluminal thrombus but also in neointimal proliferation. PAI-1 is not normally present in kidney tissue, but its concentration increases significantly in its acute and chronic kidney disease, thanks to the synthesis by the intrarenally localized inflammatory cells. In addition to genetic predisposition, the factors that directly influence the production of PAI-1 are the following: glycemia, insulin and various neurohumoral factors. It is not normally present in the kidney tissue, but its intrarenal concentration increases significantly in acute and chronic kidney diseases. Numerous studies have confirmed the significant role of PAI-1 in the development of diabetes complications. During the last decade there has been a growth of interest in the introduction of non-invasive methods or biomarkers that would assess the degree of fibrosis in the kidney. Many studies have confirmed association between kidney and heart disease. It is not only that these diseases share common risk factors, but many other mechanisms have been suggested. Plasminogen activator inhibitor -1 plays a role in the pathogenesis of endothelial damage, processes of fibrosis and thrombosis, development of diabetes complications and acute and chronic kidney diseases.