In contrast to almost all other proteinases, human tissue-type plasminogen activator (tPA) is also proteolytically active in its zymogen or single-chain form. The closely related plasminogen activator isolated from vampire bat saliva (vPA) acts exclusively in the single-chain form, lacking the requisite cleavage site for proteolytic activation. Recent structural studies on the proteolytic domains of vPA and human tPA in two- and single-chain forms reveal the mechanism of this anomalous activity. The PA-catalyzed proteolytic conversion of plasminogen to plasmin, responsible for the initiation of fibrinolysis, is fibrin-dependent; comparative structural analysis of the plasminogen activators provides clues as to the role of fibrin as cofactor.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1515/bchm.1998.379.2.95 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The tissue-plasminogen activator-challenged thromboelastography provides a comprehensive assessment of fibrinolysis in the severely injured.
J Trauma Acute Care Surg
January 2025
From the Division of Acute Care Surgery, Department of Surgery (E.R.M., T.B.M., C.M.W., H.S., R.H., C.D.B.), University of Nebraska Medical Center, Omaha, Nebraska; Department of Surgery (H.B.M.), AdventHealth Porter; Department of Surgery (E.E.M., J.G.C.), Ernest E Moore Shock Trauma Center at Denver Health, Denver; Department of Surgery (E.E.M.), University of Colorado Anschutz Medical Campus, Aurora, Colorado; Hunter College (I.M.B.), New York, New York; Sauaia Statistical Solutions, LLC (A.S.), Denver, Colorado; and Department of Cellular and Integrative Physiology (F.I.G., C.D.B.), University of Nebraska Medical Center, Omaha, Nebraska.
Background: Tissue-plasminogen activator-challenged thromboelastography (tPA-TEG) predicts massive transfusion and mortality better than conventional rapid thromboelastography (rTEG), with little concordance between their lysis values (LY30). We hypothesized that the main fibrinolytic inhibitors plasminogen activator inhibitor-1 (PAI-1) and α-2 antiplasmin (A2AP), as well as markers of fibrinolytic activation (plasmin-antiplasmin [PAP], tPA-PAI-1 complex, tPA activity), would correlate more strongly with tPA-TEG versus rTEG LY30 and may explain the recent findings of four distinct fibrinolytic phenotypes in trauma based on these two TEG methodologies.
Methods: Adult trauma patients (n = 56) had tPA-TEG, rTEG, and plasma obtained on arrival to the emergency department with institutional review board approval.
Revealing the role of cancer-associated fibroblast senescence in prognosis and immune landscape in pancreatic cancer.
iScience
January 2025
Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Cancer-associated fibroblasts (CAFs) represent a major contributor to tumor growth. Cellular senescence is a state of cell-cycle arrest characterized by a pro-inflammatory phenotype. The potential impact of CAF senescence on tumor progression and the tumor microenvironment (TME) remains to be elucidated.
View Article and Find Full Text PDFIncreased risk of coronary artery diseases in overweight and obese individuals is partially mediated by chronic inflammation: The EPICOR study.
Nutr Metab Cardiovasc Dis
December 2024
Department of Health Sciences Università Del Piemonte Orientale, via Solaroli 17, 28100 Novara and Unit of Epidemiology, Local Health Unit of Novara, Viale Roma, 7, 28100, Novara, Italy. Electronic address:
Background And Aims: It is well known that being overweight or obese is a risk factor for coronary artery disease (CAD). At the same time, belonging to these categories indirectly influences other risk factors like hypertension, diabetes or dyslipidemia also through a chronic inflammation condition. The aim of this study was to establish to which extent the effect of body mass index (BMI) on CAD risk can be explained by the chronic inflammation degree, using a statistical mediation model.
View Article and Find Full Text PDFAltered fibrin clot properties and elevated von Willebrand factor are associated with progression to permanent atrial fibrillation: A cohort study.
Eur J Clin Invest
January 2025
Department of Thromboembolic Disorders, Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland.
Background: The role of a prothrombotic state in atrial fibrillation (AF) progression to permanent arrythmia (PerAF) is unclear. Formation of denser and poorly lysable fibrin clots has been observed in AF patients also with sinus rhythm in association with higher stroke risk. We investigated whether altered fibrin clot properties and other prothrombotic state markers may contribute to AF transition to PerAF.
View Article and Find Full Text PDFWho is at risk for tPA/DNase treatment failure in empyema?-protocol to identify key predictors for early surgical intervention from a retrospective study.
J Thorac Dis
December 2024
Critical Care Medicine, Northeast Georgia Medical Center, Gainesville, GA, USA.
Background: Empyema, characterized by the accumulation of pus in the pleural cavity, poses significant treatment challenges. While intrapleural tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) therapy is effective for many patients, a substantial proportion require surgical intervention, such as video-assisted thoracoscopic surgery (VATS), following treatment failure. Identifying tPA/DNase treatment failure-associated predictors is crucial for optimizing patient management and improving outcomes.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!