Background: The lectin pathway serine protease mannan-binding lectin-associated serine protease 1 (MASP-1) has been demonstrated to be a major link between complement and coagulation, yet little is known about its interactions with the fibrinolytic system. The aim of this work was to assess the effects of MASP-1 on fibrin clot lysis in different experimental settings.
Methods: Rotational thrombelastometry was used to evaluate the effect of MASP-1 on the lysis of clots formed in whole blood under static conditions. Whole blood clots were also formed in the presence and absence of MASP-1 under flow conditions in the Chandler loop and their lysis was analysed separately by fluorescence release of incorporated labelled fibrin. Real-time observation by laser scanning confocal microscopy was used to investigate the lysis of plasma clots where MASP-1 was present either during clot formation or lysis. Cleavage of tPA or plasminogen by MASP-1 was analysed by gel electrophoresis. We performed a turbidimetric clot lysis assay in the presence and absence of the MASP-1 inhibitor SGMI-1 (Schistocerca gregaria protease inhibitor (SGPI)-based MASP inhibitor-1) to evaluate the effect of endogenous MASP-1 in normal plasma and plasma samples from sepsis patients.
Results: In the thrombelastometric experiments, where MASP-1 was present during the entire clotting and lysis process, MASP-1 had a significant profibrinolytic effect and accelerated clot lysis. When clots were formed in the presence of MASP-1 under flow in the Chandler loop, the effects on fibrinolysis were heterogenous with impaired fibrinolysis in some individuals (n = 5) and no (n = 3) or even the opposite effect (n = 2) in others. In plasma clot lysis observed by confocal microscopy, lysis was prolonged when MASP-1 was added to the lysis solution, yet there was no difference in lysis time when MASP-1 was present during clot formation. When MASP-1 was incubated with tPA or plasminogen, respectively, cleavage of single-chain tPA into two-chain tPA and a slight reduction of plasminogen were observed. SGMI-1 significantly prolonged clot lysis in the turbidimetric clot lysis assay suggesting that MASP-1 accelerated lysis in plasma samples.
Conclusion: MASP-1 is able to alter the susceptibility of blood clots to the fibrinolytic system. MASP-1 has complex, mostly promoting effects on fibrinolysis with high inter-individual variation. Interactions of MASP-1 with the fibrinolytic system may be relevant in the development and therapy of cardiovascular and thrombotic diseases.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.molimm.2019.07.005 | DOI Listing |
Front Pharmacol
December 2024
Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Introduction: In the last decades, the recombinant tissue plasminogen activator alteplase has been the standard fibrinolytic treatment of acute myocardial infarction, pulmonary embolism, and acute ischemic stroke. An optimized version of alteplase, tenecteplase, has been developed by exchanging six amino acids to increase half-life, achieve higher fibrin selectivity and increase resistance to plasminogen activator inhibitor-1. Meanwhile, several products containing tenecteplase exist.
View Article and Find Full Text PDFACS Omega
December 2024
Department of Biochemistry, Federal University of São Paulo, São Paulo, SP 04044-020, Brazil.
RMD Open
December 2024
Rheumatology, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands
Objectives: To assess the effect of treatment on haemostatic parameters in patients with early rheumatoid arthritis (RA).
Methods: Patients with newly diagnosed RA started methotrexate and were randomised to additional conventional treatment, certolizumab pegol, abatacept or tocilizumab. Several biomarkers for haemostasis were analysed including parameters of the two global haemostatic assays-overall haemostatic potential (OHP) and endogenous thrombin potential (ETP), as well as single haemostatic factors-fibrinogen, prothrombin fragment 1+2 (F1+2), D-dimer, thrombin activatable fibrinolysis inhibitor (TAFI) and clot lysis time (CLT) in 24 patients at baseline, 12 and 24 weeks after the start of the treatment.
Neurol Neurochir Pol
December 2024
Department of Thromboembolic Diseases, Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland.
Clinical Rationale For Study: We have reported that intracerebral haemorrhage (ICH) of unknown cause at a young age is associated with lower prothrombin and factor VII and higher antithrombin activity, along with the formation of looser fibrin networks displaying enhanced lysability. Patients with mild-to-moderate bleeding of unknown cause have elevated levels of free plasma tissue factor pathway inhibitor alpha (fTFPIα), inhibiting the tissue factor-factor VII complex and prothrombinase.
Aim Of Study: We hypothesised that patients with an intracerebral haemorrhage (ICH) of unknown cause may also exhibit higher fTFPIα.
Oxid Med Cell Longev
December 2024
Department of Thromboembolic Disorders, Institute of Cardiology, Jagiellonian University Medical College, 80 Pradnicka St. 31-202, Krakow, Poland.
Exercise stress test-induced hypofibrinolysis and changes in circulating levels of several interleukins have been observed in aortic stenosis (AS). However, it is unknown whether the pattern of exercise-induced changes in oxidative stress differs between AS patients and controls and if the differences are associated with changes in fibrinolysis and inflammation. We studied 32 asymptomatic patients with moderate-to-severe AS and 32 controls of similar age, sex, and body mass index.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!