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 the failure to lyse pulmonary thromboemboli is caused by the local expression of the primary inhibitor of tissue-type plasminogen activator (type 1 plasminogen activator inhibitor, PAI-1), levels of PAI-1 antigen and mRNA were analyzed by immunohistochemistry and in situ hybridization in specimens harvested from a series of patients during pulmonary thromboendarterectomies. Red, fibrin-rich thrombi within the thromboendarterectomy specimens were lined with a single layer of endothelial cells exhibiting high levels of PAI-1 antigen. Quantitation of the in situ 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 noninvolved areas of patients' pulmonary arteries (n = 16, P < .001). In contrast, tissue-type plasminogen activator antigen levels were low in all samples. Yellowish-white thrombi were composed of smooth muscle cells and endothelial cells in numerous vessels that stained prominently for PAI-1 antigen. Both types of cells within the highly organized tissues also exhibited elevated PAI-1 mRNA levels in comparison to patient pulmonary artery specimens that were free of thrombus (n = 16, P < .02).
CONCLUSIONS: The prevalence of PAI-1 expression within pulmonary thromboemboli suggests that this inhibitory may play a role in the stabilization of vascular thrombi.