EXPRESSION OF TYPE-1 PLASMINOGEN-ACTIVATOR INHIBITOR IN CHRONIC PULMONARY THROMBOEMBOLI

Background Chronic thromboembolic pulmonary hypertension is the result of nonresolving pulmonary emboli that lead to chronic obstruction of the central pulmonary arteries. Methods and Results To determine if th e failure to lyse pulmonary thromboemboli is caused by the local expre ssion of the primary inhibitor of tissue-type plasminogen activator (t ype 1 plasminogen activator inhibitor, PAI-1), levels of PAI-1 antigen and mRNA were analyzed by immunohistochemistry and in situ hybridizat ion in specimens harvested from a series of patients during pulmonary thromboendarterectomies. Red, fibrin-rich thrombi within the thromboen darterectomy specimens were lined with a single layer of endothelial c ells exhibiting high levels of PAT-1 antigen. Quantitation of the in s itu hybridization signal revealed that a significant increase in PAI-1 mRNA was present in the endothelial cells lining the fresh thrombi in comparison to the signal present in the endothelial cells from noninv olved areas of patients' pulmonary arteries (n=16, P<.001). In contras t, tissue-type plasminogen activator antigen levels were low in all sa mples. Yellowish-white thrombi were composed of smooth muscle cells an d endothelial cells in numerous vessels that stained prominently for P AI-1 antigen. Both types of cells within the highly organized tissues also exhibited elevated PAI-1 mRNA levels in comparison to patient pul monary artery specimens that were free of thrombus (n=16, P<.02). Conc lusions The prevalence of PAI-1 expression within pulmonary thromboemb oli suggests that this inhibitor may play a role in the stabilization of vascular thrombi.