The Experts below are selected from a list of 50439 Experts worldwide ranked by ideXlab platform
Yogendra Kanthi - One of the best experts on this subject based on the ideXlab platform.
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plasma tissue Plasminogen Activator and Plasminogen Activator inhibitor 1 in hospitalized covid 19 patients
Scientific Reports, 2021Co-Authors: Yu Zuo, Mark Warnock, Alyssa Harbaugh, Srilakshmi Yalavarthi, Kelsey Gockman, Melanie Zuo, Jacqueline A Madison, Jason S Knight, Yogendra KanthiAbstract:Patients with coronavirus disease-19 (COVID-19) are at high risk for thrombotic arterial and venous occlusions. However, bleeding complications have also been observed in some patients. Understanding the balance between coagulation and fibrinolysis will help inform optimal approaches to thrombosis prophylaxis and potential utility of fibrinolytic-targeted therapies. 118 hospitalized COVID-19 patients and 30 healthy controls were included in the study. We measured plasma antigen levels of tissue-type Plasminogen Activator (tPA) and Plasminogen Activator inhibitor-1 (PAI-1) and performed spontaneous clot-lysis assays. We found markedly elevated tPA and PAI-1 levels in patients hospitalized with COVID-19. Both factors demonstrated strong correlations with neutrophil counts and markers of neutrophil activation. High levels of tPA and PAI-1 were associated with worse respiratory status. High levels of tPA, in particular, were strongly correlated with mortality and a significant enhancement in spontaneous ex vivo clot-lysis. While both tPA and PAI-1 are elevated among COVID-19 patients, extremely high levels of tPA enhance spontaneous fibrinolysis and are significantly associated with mortality in some patients. These data indicate that fibrinolytic homeostasis in COVID-19 is complex with a subset of patients expressing a balance of factors that may favor fibrinolysis. Further study of tPA as a biomarker is warranted.
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plasma tissue Plasminogen Activator and Plasminogen Activator inhibitor 1 in hospitalized covid 19 patients
medRxiv, 2020Co-Authors: Yu Zuo, Mark Warnock, Alyssa Harbaugh, Srilakshmi Yalavarthi, Kelsey Gockman, Melanie Zuo, Jacqueline A Madison, Jason S Knight, Yogendra KanthiAbstract:ABSTRACT Patients with coronavirus disease-19 (COVID-19) are at high risk for thrombotic arterial and venous occlusions. However, bleeding complications have also been observed in some patients. Understanding the balance between coagulation and fibrinolysis will help inform optimal approaches to thrombosis prophylaxis and potential utility of fibrinolytic-targeted therapies. 118 hospitalized COVID-19 patients and 30 healthy controls were included in the study. We measured plasma antigen levels of tissue-type Plasminogen Activator (tPA) and Plasminogen Activator inhibitor-1 (PAI-1) and performed spontaneous clot-lysis assays. We found markedly elevated tPA and PAI-1 levels in patients hospitalized with COVID-19. Both factors demonstrated strong correlations with neutrophil counts and markers of neutrophil activation. High levels of tPA and PAI-1 were associated with worse respiratory status. High levels of tPA, in particular, were strongly correlated with mortality and a significant enhancement in spontaneous ex vivo clot-lysis. While both tPA and PAI-1 are elevated among COVID-19 patients, extremely high levels of tPA enhance spontaneous fibrinolysis and are significantly associated with mortality in some patients. These data indicate that fibrinolytic homeostasis in COVID-19 is complex with a subset of patients expressing a balance of factors that may favor fibrinolysis, and suggests that further study of tPA as a biomarker is warranted.
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plasma tissue Plasminogen Activator and Plasminogen Activator inhibitor 1 in hospitalized covid 19 patients
medRxiv, 2020Co-Authors: Yu Zuo, Mark Warnock, Alyssa Harbaugh, Srilakshmi Yalavarthi, Kelsey Gockman, Melanie Zuo, Jacqueline A Madison, Jason S Knight, Yogendra KanthiAbstract:Background: Patients with coronavirus disease 19 (COVID-19) are at high risk for thrombotic arterial and venous occlusions, while lung histopathology often reveals fibrin-based occlusion of small vessels in patients who succumb to the disease. At the same time, bleeding complications have been observed in some patients. Better understanding the balance between coagulation and fibrinolysis will help inform optimal approaches to thrombosis prophylaxis and potential utility of fibrinolytic-targeted therapies. Objective: To evaluate fibrinolysis among a large cohort of hospitalized COVID-19 patients. Patients and methods: 118 hospitalized COVID-19 patients and 30 healthy controls were included in the study. We measured plasma antigen levels of tissue-type Plasminogen Activator (tPA) and Plasminogen Activator inhibitor-1 (PAI-1) and performed spontaneous clot lysis assays. Results: We found markedly elevated levels of tPA and PAI-1 among patients hospitalized with COVID-19. Both factors demonstrated a strong correlation with neutrophil counts and markers of neutrophil activation, but not with D-dimer. High levels of tPA and PAI-1 were associated with worse respiratory status. High levels of tPA, in particular, were also strongly correlated with mortality and with a significant enhancement in spontaneous ex vivo clot lysis. Conclusion: While both tPA and PAI-1 are elevated among COVID-19 patients, extremely high levels of tPA enhance spontaneous fibrinolysis and are significantly associated with mortality in some patients. These data indicate that fibrinolytic homeostasis in COVID-19 is complex with a subset of patients expressing a balance of factors that may favor fibrinolysis and suggests that further study of tPA as a potential biomarker is warranted.
Bernard Degryse - One of the best experts on this subject based on the ideXlab platform.
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vitronectin inhibits Plasminogen Activator inhibitor 1 induced signalling and chemotaxis by blocking Plasminogen Activator inhibitor 1 binding to the low density lipoprotein receptor related protein
The International Journal of Biochemistry & Cell Biology, 2009Co-Authors: Yuichi Kamikubo, Jaap G Neels, Bernard DegryseAbstract:We have previously reported that the serpin Plasminogen Activator inhibitor-1 activates the Janus kinase (Jak)/signal transducer and Activator of transcription (Stat) signalling pathway and stimulates cell migration by binding to the low-density lipoprotein receptor-related protein. All the free forms (cleaved, latent or active) of this inhibitor were shown to be motogenic. However, the Plasminogen Activator inhibitor-1 can also interact with vitronectin which acts as a cofactor by increasing the half-life of the active form of the serpin. Since vitronectin influences most of the biological functions of the Plasminogen Activator inhibitor-1, we explored the effects of vitronectin on signalling and cell migration induced by this serpin. We found that the interaction between vitronectin and the Plasminogen Activator inhibitor-1 suppressed signalling and cell migration. In fact, a purified vitronectin(1-97)/Plasminogen Activator inhibitor-1 complex was not chemotactic. Vitronectin interaction with the Plasminogen Activator inhibitor-1 blocks the binding of this serpin to its motogenic receptor, the low-density lipoprotein receptor-related protein. Consequently, vitronectin inhibits the activation of the Janus kinase/signal transducer and Activator of transcription signalling pathway by the Plasminogen Activator inhibitor-1 and subsequent cell migration. In conclusion, we have unveiled a new inhibitory role of vitronectin, which turns off the intracellular signalling and migration-promoting activity of the Plasminogen Activator inhibitor-1. Thus, the motogenic (cleaved, latent or active) and non-motogenic (in complex with vitronectin) forms of the Plasminogen Activator inhibitor-1 have different properties that may explain the rather contrasting physiological and pathological roles of this serpin.
Joachim Herz - One of the best experts on this subject based on the ideXlab platform.
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complexes of tissue type Plasminogen Activator and its serpin inhibitor Plasminogen Activator inhibitor type 1 are internalized by means of the low density lipoprotein receptor related protein α2 macroglobulin receptor
Proceedings of the National Academy of Sciences of the United States of America, 1992Co-Authors: Kim Orth, Edwin L Madison, Mary Jane Gething, Joseph Sambrook, Joachim HerzAbstract:Abstract Tissue-type Plasminogen Activator and urokinase are serine proteases secreted by many cell types that participate in biological processes, such as tissue restructuring, cell migration, and tumor metastasis. Clinically, these proteases are used to dissolve coronary fibrin clots that are the proximal causes of acute myocardial infarction. In vivo, the activity of these enzymes is controlled by Plasminogen-Activator inhibitors, members of the serpin family of protease inhibitors. This study shows that tissue-type Plasminogen Activator-inhibitor complexes bind in solution to low density lipoprotein receptor-related protein (LRP), a large heterodimeric ubiquitous membrane receptor. In cultured cells, endocytosis and degradation of these complexes is reduced by polyclonal antibodies directed against LRP and inhibited by a M(r) 39,000 protein that binds to LRP and inhibits its interaction with previously known ligands, including apolipoprotein E and alpha 2-macroglobulin. We propose a role for LRP in the clearance of Plasminogen Activator-inhibitor complexes that is analogous to its function in the endocytosis of alpha 2-macroglobulin-protease complexes.
Mary Jane Gething - One of the best experts on this subject based on the ideXlab platform.
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complexes of tissue type Plasminogen Activator and its serpin inhibitor Plasminogen Activator inhibitor type 1 are internalized by means of the low density lipoprotein receptor related protein α2 macroglobulin receptor
Proceedings of the National Academy of Sciences of the United States of America, 1992Co-Authors: Kim Orth, Edwin L Madison, Mary Jane Gething, Joseph Sambrook, Joachim HerzAbstract:Abstract Tissue-type Plasminogen Activator and urokinase are serine proteases secreted by many cell types that participate in biological processes, such as tissue restructuring, cell migration, and tumor metastasis. Clinically, these proteases are used to dissolve coronary fibrin clots that are the proximal causes of acute myocardial infarction. In vivo, the activity of these enzymes is controlled by Plasminogen-Activator inhibitors, members of the serpin family of protease inhibitors. This study shows that tissue-type Plasminogen Activator-inhibitor complexes bind in solution to low density lipoprotein receptor-related protein (LRP), a large heterodimeric ubiquitous membrane receptor. In cultured cells, endocytosis and degradation of these complexes is reduced by polyclonal antibodies directed against LRP and inhibited by a M(r) 39,000 protein that binds to LRP and inhibits its interaction with previously known ligands, including apolipoprotein E and alpha 2-macroglobulin. We propose a role for LRP in the clearance of Plasminogen Activator-inhibitor complexes that is analogous to its function in the endocytosis of alpha 2-macroglobulin-protease complexes.
Karluwe Petersen - One of the best experts on this subject based on the ideXlab platform.
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ppack desmodus rotundus salivary Plasminogen Activator cdspaα1 prevents the passage of tissuetype Plasminogen Activator rt pa across the blood brain barrier and neurotoxicity
Thrombosis and Haemostasis, 2009Co-Authors: Benoit D Roussel, Karluwe Petersen, Yannick Hommet, Richard Macrez, Torsten Schulz, Vincent Berezowski, Romeo Cecchelli, Carine Ali, Denis VivienAbstract:PPACK-Desmodus rotundus salivary Plasminogen Activator (cDSPAα1) prevents the passage of tissuetype Plasminogen Activator (rt-PA) across the blood-brain barrier and neurotoxicity -
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vampire bat salivary Plasminogen Activator desmoteplase inhibits tissue type Plasminogen Activator induced potentiation of excitotoxic injury
Stroke, 2005Co-Authors: Courtney Reddrop, Randal X Moldrich, Philip M Beart, Mark C Farso, Gabriel T Liberatore, David W Howells, Karluwe Petersen, Robert L MedcalfAbstract:Background and Purpose— In contrast to tissue-type Plasminogen Activator (tPA), vampire bat (Desmodus rotundus) salivary Plasminogen Activator (desmoteplase [DSPA]) does not promote excitotoxic injury when injected directly into the brain. We have compared the excitotoxic effects of intravenously delivered tPA and DSPA and determined whether DSPA can antagonize the neurotoxic and calcium enhancing effects of tPA. Methods— The brain striatal region of wild-type c57 Black 6 mice was stereotaxically injected with N-methyl-d-Aspartate (NMDA); 24 hour later, mice received an intravenous injection of tPA or DSPA (10 mg/kg) and lesion size was assessed after 24 hours. Cell death and calcium mobilization studies were performed using cultures of primary murine cortical neurons. Results— NMDA-mediated injury was increased after intravenous administration of tPA, whereas no additional toxicity was seen after administration of DSPA. Unlike DSPA, tPA enhanced NMDA-induced cell death and the NMDA-mediated increase in i...