ELEVATED EXPRESSION OF UROKINASE-LIKE PLASMINOGEN-ACTIVATOR AND PLASMINOGEN-ACTIVATOR INHIBITOR TYPE-1 DURING THE VASCULAR REMODELING ASSOCIATED WITH PULMONARY THROMBOEMBOLISM

Information is lacking on the mechanisms involved in the organization, resolution, and repair of the vascular lumen after acute pulmonary th romboembolism. Because recent data suggest that the balance between pl asminogen activators (PAs) and type 1 plasminogen activator inhibitor (PAI-1) plays a role in regulating cell migration within the extracell ular matrix, we investigated the expression of these molecules by immu nohistochemical and in situ hybridization analysis of pulmonary artery specimens from patients suffering fatal pulmonary embolism. The data were compared with the expression of these molecules in both patients' noninvolved pulmonary arteries and organ donor pulmonary arteries. Re gions of initial organization and vascular remodeling were identified by a modified trichrome stain and by the presence of proliferating cel l nuclear antigen (PCNA), a cell marker of proliferation. Staining for tissue-type PA antigen was low to undetectable in endothelial cells d irectly in contact with the fibrin-platelet thromboembolus and in area s in which the endothelial cell lining was replaced by cell growth int o the thrombus. Urokinase-like PA (u-PA) expression was detected in mo nonuclear cells within the thrombus in the initial phase of thromboemb olism and within cells migrating into the thrombus during the later st ages of organization. PAI-1 expression was elevated in the monolayer o f endothelial cells underlying the fresh platelet-fibrin thromboembolu s and in a PCNA-positive cell population present between the pulmonary arterial intima and the thromboembolus that represents early organiza tion. Increased expression of PAI-1 may play a role in inhibiting prot eolysis and fostering the localization of the acute fibrin-platelet th rombus to the vascular wall, which is followed by the upregulation of u-PA in migrating cells during the reorganization process.