Expression of type 1 plasminogen activator inhibitor in chronic pulmonary thromboemboli.
نویسندگان
چکیده
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.
منابع مشابه
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 an abnormality in the endothelial cell (EC)-associated fibrinolytic system, conditions were established to culture ECs from patient ...
متن کاملSuppression of thrombolysis in a canine model of pulmonary embolism.
BACKGROUND The brisk fibrinolytic response of canines has impaired efforts to develop a canine model of chronic thromboembolic pulmonary hypertension. Difficulties in retaining chronic embolic residuals were partially overcome by administration of tranexamic acid (TXA) (Circulation. 1991;83:1272-1279.). In this study, we used type 1 plasminogen activator inhibitor (PAI-1), a major inhibitor of ...
متن کاملSerum Level of Plasminogen Activator Inhibitor Type-1 in Addicted Patients with Coronary Artery Disease
Background: Plasminogen activator inhibitor-1 (PAI-1) is a glycoprotein with inhibitory effects on the formation of plasmin from plasminogen by plasminogen activator. Thus, it prevents clot lysis in vessel walls. Several evidences prove the relationship between coronary artery disease and response to fibrinolytic therapy in patients with myocardial infarction with PAI-1 level. Opium addiction i...
متن کاملMethyltetrahydrofolate Reductase C677T Mutation and 4G/5G Plasminogen Activator Inhibitor-1 Polymorphism in a Child with Deep Vein Thrombosis
متن کامل
Nickel requires hypoxia-inducible factor-1a, not redox signaling, to induce plasminogen activator inhibitor-1
Andrew, Angeline S., Linda R. Klei, and Aaron Barchowsky. Nickel requires hypoxia-inducible factor-1a, not redox signaling, to induce plasminogen activator inhibitor-1. Am J Physiol Lung Cell Mol Physiol 281: L607–L615, 2001.—Human epidemiological and animal studies have associated inhalation of nickel dusts with an increased incidence of pulmonary fibrosis. At the cellular level, particulate n...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Circulation
دوره 89 6 شماره
صفحات -
تاریخ انتشار 1994