Parallel analysis of tissue-type plasminogen activator and type 1 plasminogen activator inhibitor in plasma and endothelial cells derived from patients with chronic pulmonary thromboemboli.

Abstract

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 an abnormality in the endothelial cell (EC)-associated fibrinolytic system, conditions were established to culture ECs from patient main pulmonary arteries during surgical pulmonary thromboendarterectomies and to analyze the conditioned media for levels of tissue-type plasminogen activator (TPA) and type 1 plasminogen activator inhibitor (PAI-1). Our data indicate that the levels of TPA antigen and PAI-1 activity in media conditioned by primary ECs harvested from areas free of thrombus were not significantly different between patients with chronic thromboemboli and organ donors. In 13 consecutive patients, no correlation was obtained in either the TPA antigen or PAI-1 activity level in a patient's plasma and the respective levels in media conditioned by the patient's pulmonary ECs. Moreover, patient pulmonary arterial ECs were observed to increase the secretion of TPA and PAI-1 in response to thrombin in a fashion similar to donor pulmonary artery ECs. CONCLUSIONS The data suggest that an inherent EC-mediated fibrinolytic imbalance is not a generalized phenomenon observed in pulmonary arteries of patients with chronic pulmonary thromboemboli.