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Article ; Online: MicroRNA-10a enrichment in factor VIIa-released endothelial extracellular vesicles: potential mechanisms.

Das, Kaushik / Keshava, Shiva / Kolesnick, Richard / Pendurthi, Usha R / Rao, L Vijaya Mohan

Journal of thrombosis and haemostasis : JTH

2023 Volume 22, Issue 2, Page(s) 441–454

Abstract: Background: Factor VIIa induces the release of extracellular vesicles (EVs) from endothelial cells (EEVs). Factor VIIa-released EEVs are enriched with microRNA-10a (miR10a) and elicit miR10a-dependent cytoprotective responses.: Objectives: To ... ...

Abstract	Background: Factor VIIa induces the release of extracellular vesicles (EVs) from endothelial cells (EEVs). Factor VIIa-released EEVs are enriched with microRNA-10a (miR10a) and elicit miR10a-dependent cytoprotective responses. Objectives: To investigate mechanisms by which FVIIa induces miR10a expression in endothelial cells and sorts miR10a into the EVs. Methods: Activation of Elk-1 and TWIST1 expression was analyzed by immunofluorescence microscopy and immunoblot analysis. Small interfering RNA silencing approach was used to knock down the expression of specific genes in endothelial cells. EVs secreted from endothelial cells or released into circulation in mice were isolated by centrifugation and quantified by nanoparticle tracking analysis. Factor VIIa or EVs were injected into mice; mice were challenged with lipopolysaccharides to assess the cytoprotective effects of FVIIa or EVs. Results: FVIIa activation of ERK1/2 triggered the activation of Elk-1, which led to the induction of TWIST1, a key transcription factor involved in miR10a expression. Factor VIIa also induced the expression of La, a small RNA-binding protein. Factor VIIa-driven acid sphingomyelinase (ASM) activation and the subsequent activation of the S1P receptor pathway were responsible for the induction of La. Silencing of ASM or La significantly reduced miR10a levels in FVIIa-released EEVs without affecting the cellular expression of miR10a. Factor VIIa-EEVs from ASM knocked-down cells failed to provide cytoprotective responses in cell and murine model systems. Administration of FVIIa protected wild-type but not ASM Conclusion: Our data suggest that enhanced cellular expression of miR10a coupled with La-dependent sorting of miR10a is responsible for enriching FVIIa-released EVs with miR10a.
MeSH term(s)	Mice ; Animals ; Factor VIIa/metabolism ; Endothelial Cells/metabolism ; Signal Transduction ; Lipopolysaccharides/metabolism ; Extracellular Vesicles/metabolism ; MicroRNAs/genetics ; MicroRNAs/metabolism
Chemical Substances	Factor VIIa (EC 3.4.21.21) ; Lipopolysaccharides ; MicroRNAs
Language	English
Publishing date	2023-11-04
Publishing country	England
Document type	Journal Article
ZDB-ID	2112661-6
ISSN	1538-7836 ; 1538-7933
ISSN (online)	1538-7836
ISSN	1538-7933
DOI	10.1016/j.jtha.2023.10.021
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Article ; Online: Factor VIIa releases phosphatidylserine-enriched extracellular vesicles from endothelial cells by activating acid sphingomyelinase.

Das, Kaushik / Keshava, Shiva / Mukherjee, Tanmoy / Wang, Jue / Magisetty, Jhansi / Kolesnick, Richard / Pendurthi, Usha R / Rao, L Vijaya Mohan

Journal of thrombosis and haemostasis : JTH

2023 Volume 21, Issue 12, Page(s) 3414–3431

Abstract: Background: Our recent studies showed that activated factor (F) VII (FVIIa) releases extracellular vesicles (EVs) from the endothelium. FVIIa-released EVs were found to be enriched with phosphatidylserine (PS) and contribute to the hemostatic effect of ... ...

Abstract	Background: Our recent studies showed that activated factor (F) VII (FVIIa) releases extracellular vesicles (EVs) from the endothelium. FVIIa-released EVs were found to be enriched with phosphatidylserine (PS) and contribute to the hemostatic effect of FVIIa in thrombocytopenia and hemophilia. Objective: To investigate mechanisms by which FVIIa induces EV biogenesis and enriches EVs with PS. Methods: FVIIa activation of acid sphingomyelinase (aSMase) was evaluated by its translocation to the cell surface. The role of aSMase in the biogenesis of FVIIa-induced EVs and their enrichment with PS was investigated using specific siRNAs and inhibitors of aSMase and its downstream metabolites. Wild-type and aSMase Results: FVIIa activation of aSMase is responsible for both the externalization of PS and the release of EVs in endothelial cells. FVIIa-induced aSMase activation led to ceramide generation and de novo expression of transmembrane protein 16F. Inhibitors of ceramidases, sphingosine kinase, or sphingosine-1-phosphate receptor modulator blocked FVIIa-induced expression of transmembrane protein 16F and PS externalization without interfering with FVIIa release of EVs. In vivo, FVIIa release of EVs was markedly impaired in aSMase Conclusion: Our study identifies a novel mechanism by which FVIIa induces PS externalization and releases PS-enriched EVs.
MeSH term(s)	Animals ; Mice ; Endothelial Cells/metabolism ; Extracellular Vesicles/metabolism ; Factor VIIa/metabolism ; Hemostatics ; Phosphatidylserines/metabolism ; Sphingomyelin Phosphodiesterase/metabolism ; Thrombocytopenia/metabolism
Chemical Substances	Factor VIIa (EC 3.4.21.21) ; Hemostatics ; Phosphatidylserines ; Sphingomyelin Phosphodiesterase (EC 3.1.4.12) ; ASMase, mouse (EC 3.1.4.12)
Language	English
Publishing date	2023-10-22
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2112661-6
ISSN	1538-7836 ; 1538-7933
ISSN (online)	1538-7836
ISSN	1538-7933
DOI	10.1016/j.jtha.2023.08.025
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Article ; Online: Factor VIIa suppresses inflammation and barrier disruption through the release of EEVs and transfer of microRNA 10a.

Das, Kaushik / Keshava, Shiva / Pendurthi, Usha R / Rao, L Vijaya Mohan

Blood

2021 Volume 139, Issue 1, Page(s) 118–133

Abstract: Coagulation protease, factor VIIa (FVIIa), binds to endothelial cell protein C receptor (EPCR) and induces anti-inflammatory and endothelial barrier protective responses via protease-activated receptor-1 (PAR1)-mediated, biased signaling. Our recent ... ...

Abstract	Coagulation protease, factor VIIa (FVIIa), binds to endothelial cell protein C receptor (EPCR) and induces anti-inflammatory and endothelial barrier protective responses via protease-activated receptor-1 (PAR1)-mediated, biased signaling. Our recent studies had shown that the FVIIa-EPCR-PAR1 axis induces the release of extracellular vesicles (EVs) from endothelial cells. In the present study, we investigated the mechanism of FVIIa release of endothelial EVs (EEVs) and the contribution of FVIIa-released EEVs to anti-inflammatory and vascular barrier protective effects, in both in vitro and in vivo models. Multiple signaling pathways regulated FVIIa release of EVs from endothelial cells, but the ROCK-dependent pathway appeared to be a major mechanism. FVIIa-released EEVs were enriched with anti-inflammatory microRNAs (miRs), mostly miR10a. FVIIa-released EEVs were taken up readily by monocytes/macrophages and endothelial cells. The uptake of FVIIa-released EEVs by monocytes conferred anti-inflammatory phenotype to monocytes, whereas EEV uptake by endothelial cells resulted in barrier protection. In additional experiments, EEV-mediated delivery of miR10a to monocytes downregulated the expression of TAK1 and activation of the NF-κB-mediated inflammatory pathway. In in vivo experiments, administration of FVIIa-released EEVs to wild-type mice attenuated LPS-induced increased inflammatory cytokines in plasma and vascular leakage into vital tissues. The incorporation of anti-miR10a into FVIIa-released EEVs diminished the ability of FVIIa-released EEVs to confer cytoprotective effects. Administration of the ROCK inhibitor Y27632, which significantly inhibits FVIIa release of EEVs into the circulation, to mice attenuated the cytoprotective effects of FVIIa. Overall, our study revealed novel insights into how FVIIa induces cytoprotective effects and communicates with various cell types.
MeSH term(s)	Animals ; Endothelial Cells/metabolism ; Extracellular Vesicles/metabolism ; Factor VIIa/metabolism ; Human Umbilical Vein Endothelial Cells ; Humans ; Inflammation/metabolism ; Mice, Inbred C57BL ; MicroRNAs/metabolism ; Monocytes/metabolism ; THP-1 Cells ; Mice
Chemical Substances	MIRN10 microRNA, human ; MicroRNAs ; Factor VIIa (EC 3.4.21.21)
Language	English
Publishing date	2021-09-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2021012358
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Article ; Online: SARS-CoV-2 infection induces the activation of tissue factor-mediated coagulation via activation of acid sphingomyelinase.

Wang, Jue / Pendurthi, Usha R / Yi, Guohua / Rao, L Vijaya Mohan

Blood

2021 Volume 138, Issue 4, Page(s) 344–349

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with the hypercoagulable state. Tissue factor (TF) is the primary cellular initiator of coagulation. Most of the TF expressed on cell surfaces remains cryptic. ... ...

Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with the hypercoagulable state. Tissue factor (TF) is the primary cellular initiator of coagulation. Most of the TF expressed on cell surfaces remains cryptic. Sphingomyelin (SM) is responsible for maintaining TF in the encrypted state, and hydrolysis of SM by acid sphingomyelinase (ASMase) increases TF activity. ASMase was shown to play a role in virus infection biology. In the present study, we investigated the role of ASMase in SARS-CoV-2 infection-induced TF procoagulant activity. Infection of human monocyte-derived macrophages (MDMs) with SARS-CoV-2 spike protein pseudovirus (SARS-CoV-2-SP-PV) markedly increased TF procoagulant activity at the cell surface and released TF+ extracellular vesicles. The pseudovirus infection did not increase either TF protein expression or phosphatidylserine externalization. SARS-CoV-2-SP-PV infection induced the translocation of ASMase to the outer leaflet of the plasma membrane, which led to the hydrolysis of SM in the membrane. Pharmacologic inhibitors or genetic silencing of ASMase attenuated SARS-CoV-2-SP-PV-induced increased TF activity. Inhibition of the SARS-CoV-2 receptor, angiotensin-converting enzyme-2, attenuated SARS-CoV-2-SP-PV-induced increased TF activity. Overall, our data suggest that SARS-CoV-2 infection activates the coagulation by decrypting TF through activation of ASMase. Our data suggest that the US Food and Drug Administration-approved functional inhibitors of ASMase may help treat hypercoagulability in patients with COVID-19.
MeSH term(s)	Angiotensin-Converting Enzyme 2/physiology ; COVID-19/blood ; COVID-19/complications ; Cell-Derived Microparticles ; Enzyme Activation ; Humans ; Hydrolysis ; Macrophages/enzymology ; Macrophages/virology ; Membrane Proteins/physiology ; Molecular Targeted Therapy ; Plasmids ; Protein Transport ; RNA Interference ; RNA, Small Interfering/genetics ; Receptors, Virus/physiology ; SARS-CoV-2 ; Sphingomyelin Phosphodiesterase/antagonists & inhibitors ; Sphingomyelin Phosphodiesterase/physiology ; Sphingomyelins/physiology ; Spike Glycoprotein, Coronavirus/physiology ; Thrombophilia/blood ; Thrombophilia/drug therapy ; Thrombophilia/enzymology ; Thrombophilia/etiology ; Thromboplastin/physiology
Chemical Substances	Membrane Proteins ; RNA, Small Interfering ; Receptors, Virus ; Sphingomyelins ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Thromboplastin (9035-58-9) ; SMPD1 protein, human (EC 3.1.4.12) ; Sphingomyelin Phosphodiesterase (EC 3.1.4.12) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Language	English
Publishing date	2021-04-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2021010685
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Article ; Online: The Gab2-MALT1 axis regulates thromboinflammation and deep vein thrombosis.

Kondreddy, Vijay / Keshava, Shiva / Das, Kaushik / Magisetty, Jhansi / Rao, L Vijaya Mohan / Pendurthi, Usha R

Blood

2022 Volume 140, Issue 13, Page(s) 1549–1564

Abstract: Deep vein thrombosis (DVT) is the third most common cause of cardiovascular mortality. Several studies suggest that DVT occurs at the intersection of dysregulated inflammation and coagulation upon activation of inflammasome and secretion of interleukin ... ...

Abstract	Deep vein thrombosis (DVT) is the third most common cause of cardiovascular mortality. Several studies suggest that DVT occurs at the intersection of dysregulated inflammation and coagulation upon activation of inflammasome and secretion of interleukin 1β (IL-1β) in restricted venous flow conditions. Our recent studies showed a signaling adapter protein, Gab2 (Grb2-associated binder 2), plays a crucial role in propagating inflammatory signaling triggered by IL-1β and other inflammatory mediators in endothelial cells. The present study shows that Gab2 facilitates the assembly of the CBM (CARMA3 [CARD recruited membrane-associated guanylate kinase protein 3]-BCL-10 [B-cell lymphoma 10]-MALT1 [mucosa-associated lymphoid tissue lymphoma translocation protein 1]) signalosome, which mediates the activation of Rho and NF-κB in endothelial cells. Gene silencing of Gab2 or MALT1, the effector signaling molecule in the CBM signalosome, or pharmacological inhibition of MALT1 with a specific inhibitor, mepazine, significantly reduced IL-1β-induced Rho-dependent exocytosis of P-selectin and von Willebrand factor (VWF) and the subsequent adhesion of neutrophils to endothelial cells. MALT1 inhibition also reduced IL-1β-induced NF-κB-dependent expression of tissue factor and vascular cell adhesion molecule 1. Consistent with the in vitro data, Gab2 deficiency or pharmacological inhibition of MALT1 suppressed the accumulation of monocytes and neutrophils at the injury site and attenuated venous thrombosis induced by the inferior vena cava ligation-induced stenosis or stasis in mice. Overall, our data reveal a previously unrecognized role of the Gab2-MALT1 axis in thromboinflammation. Targeting the Gab2-MALT1 axis with MALT1 inhibitors may become an effective strategy to treat DVT by suppressing thromboinflammation without inducing bleeding complications.
MeSH term(s)	Adaptor Proteins, Signal Transducing ; Animals ; B-Cell CLL-Lymphoma 10 Protein/metabolism ; CARD Signaling Adaptor Proteins/metabolism ; Endothelial Cells/metabolism ; Guanylate Kinases/metabolism ; Inflammasomes/metabolism ; Inflammation ; Inflammation Mediators ; Interleukin-1beta/metabolism ; Mice ; Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein/genetics ; NF-kappa B/metabolism ; P-Selectin/metabolism ; Thromboinflammation ; Thromboplastin/metabolism ; Thrombosis ; Vascular Cell Adhesion Molecule-1/metabolism ; Venous Thrombosis/genetics ; von Willebrand Factor/metabolism
Chemical Substances	Adaptor Proteins, Signal Transducing ; B-Cell CLL-Lymphoma 10 Protein ; CARD Signaling Adaptor Proteins ; Gab2 protein, mouse ; Inflammasomes ; Inflammation Mediators ; Interleukin-1beta ; NF-kappa B ; P-Selectin ; Vascular Cell Adhesion Molecule-1 ; von Willebrand Factor ; Thromboplastin (9035-58-9) ; Guanylate Kinases (EC 2.7.4.8) ; Malt1 protein, mouse (EC 3.4.22.-) ; Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein (EC 3.4.22.-)
Language	English
Publishing date	2022-07-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2022016424
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Article ; Online: Size matters for polyP to clot.

Pendurthi, Usha R

Blood

2010 Volume 116, Issue 20, Page(s) 4042–4043

Language	English
Publishing date	2010-11-18
Publishing country	United States
Document type	Comment ; Journal Article
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2010-09-305151
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Article ; Online: Factor VIIa treatment increases circulating extracellular vesicles in hemophilia patients: Implications for the therapeutic hemostatic effect of FVIIa.

Das, Kaushik / Pendurthi, Usha R / Manco-Johnson, Marylyn / Martin, Erika J / Brophy, Donald F / Rao, L Vijaya Mohan

Journal of thrombosis and haemostasis : JTH

2022 Volume 20, Issue 8, Page(s) 1928–1933

MeSH term(s)	Extracellular Vesicles ; Factor VIIa/pharmacology ; Factor VIIa/therapeutic use ; Hemophilia A/drug therapy ; Hemostasis ; Hemostatics/therapeutic use ; Humans
Chemical Substances	Hemostatics ; Factor VIIa (EC 3.4.21.21)
Language	English
Publishing date	2022-06-06
Publishing country	England
Document type	Letter ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2112661-6
ISSN	1538-7836 ; 1538-7933
ISSN (online)	1538-7836
ISSN	1538-7933
DOI	10.1111/jth.15768
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Article ; Online: Role of Cell Surface Lipids and Thiol-Disulphide Exchange Pathways in Regulating the Encryption and Decryption of Tissue Factor.

Ansari, Shabbir A / Pendurthi, Usha R / Rao, L Vijaya Mohan

Thrombosis and haemostasis

2019 Volume 119, Issue 6, Page(s) 860–870

Abstract: Tissue factor (TF), a transmembrane glycoprotein, is the cellular receptor of the coagulation factors VII (FVII) and VIIa (FVIIa). The formation of TF-FVIIa complex triggers the initiation of the blood coagulation pathway. TF plays an essential role in ... ...

Abstract	Tissue factor (TF), a transmembrane glycoprotein, is the cellular receptor of the coagulation factors VII (FVII) and VIIa (FVIIa). The formation of TF-FVIIa complex triggers the initiation of the blood coagulation pathway. TF plays an essential role in haemostasis, but an aberrant expression of TF activity contributes to thrombotic disorders. In health, TF pro-coagulant activity on cells is controlled tightly to allow sufficient coagulant activity to achieve haemostasis but not to cause thrombosis. It is achieved largely by selective localization of TF in the body and encryption of TF at the cell surface. A vast majority of TF on resting cells exists in an encrypted state with minimal pro-coagulant activity but becomes pro-thrombotic following cell injury or activation. At present, the mechanisms that are responsible for TF encryption and activation (decryption) are not entirely clear, but recent studies provide important mechanistic insights into these processes. To date, externalization of phosphatidylserine to the outer leaflet and thiol-disulphide exchange pathways that either turn on and off the allosteric disulphide bond in TF are shown to play a major role in regulating TF pro-coagulant activity on cell surfaces. Recent studies showed that sphingomyelin, a major phospholipid in the outer leaflet of plasma membrane, plays a critical role in the encryption of TF in resting cells. The present review provides an overview of recent literature on the above-described mechanisms of TF encryption and decryption with a particular emphasis on our recent findings.
MeSH term(s)	Animals ; Blood Coagulation ; Disulfides/metabolism ; Gene Expression Regulation ; Hemostasis ; Humans ; Membrane Lipids/metabolism ; Protein Disulfide Reductase (Glutathione)/metabolism ; Protein Disulfide-Isomerases/metabolism ; Signal Transduction ; Sulfhydryl Compounds/metabolism ; Thromboplastin/genetics ; Thromboplastin/metabolism
Chemical Substances	Disulfides ; Membrane Lipids ; Sulfhydryl Compounds ; Thromboplastin (9035-58-9) ; Protein Disulfide Reductase (Glutathione) (EC 1.8.4.2) ; Protein Disulfide-Isomerases (EC 5.3.4.1)
Language	English
Publishing date	2019-03-12
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	518294-3
ISSN	2567-689X ; 0340-6245
ISSN (online)	2567-689X
ISSN	0340-6245
DOI	10.1055/s-0039-1681102
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Uh III Zs.192: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Acid sphingomyelinase plays a critical role in LPS- and cytokine-induced tissue factor procoagulant activity.

Wang, Jue / Pendurthi, Usha R / Rao, L Vijaya Mohan

Blood

2019 Volume 134, Issue 7, Page(s) 645–655

Abstract: Tissue factor (TF) is a cofactor for factor VIIa and the primary cellular initiator of coagulation. Typically, most TF on cell surfaces exists in a cryptic coagulant-inactive state but are transformed to a procoagulant form (decryption) following cell ... ...

Abstract	Tissue factor (TF) is a cofactor for factor VIIa and the primary cellular initiator of coagulation. Typically, most TF on cell surfaces exists in a cryptic coagulant-inactive state but are transformed to a procoagulant form (decryption) following cell activation. Our recent studies in cell model systems showed that sphingomyelin (SM) in the outer leaflet of the plasma membrane is responsible for maintaining TF in an encrypted state in resting cells, and the hydrolysis of SM leads to decryption of TF. The present study was carried out to investigate the relevance of this novel mechanism in the regulation of TF procoagulant activity in pathophysiology. As observed in cell systems, administration of adenosine triphosphate (ATP) to mice enhanced lipopolysaccharide (LPS)-induced TF procoagulant activity in monocytes. Treatment of mice with pharmacological inhibitors of acid sphingomyelinase (ASMase), desipramine and imipramine, attenuated ATP-induced TF decryption. Interestingly, ASMase inhibitors also blocked LPS-induced TF procoagulant activity without affecting the LPS-induced de novo synthesis of TF protein. Additional studies showed that LPS induced translocation of ASMase to the outer leaflet of the plasma membrane and reduced SM levels in monocytes. Studies using human monocyte-derived macrophages and endothelial cells further confirmed the role of ASMase in LPS- and cytokine-induced TF procoagulant activity. Overall, our data indicate that LPS- or cytokine-induced TF procoagulant activity requires the decryption of newly synthesized TF protein by ASMase-mediated hydrolysis of SM. The observation that ASMase inhibitors attenuate TF-induced coagulation raises the possibility of their therapeutic use in treating thrombotic disorders associated with aberrant expression of TF.
MeSH term(s)	Animals ; Blood Coagulation ; Cytokines/metabolism ; Human Umbilical Vein Endothelial Cells ; Humans ; Lipopolysaccharides/metabolism ; Mice, Inbred C57BL ; Monocytes/metabolism ; Sphingomyelin Phosphodiesterase/metabolism ; Thrombin/metabolism ; Thromboplastin/metabolism ; Thrombosis/metabolism
Chemical Substances	Cytokines ; Lipopolysaccharides ; Thromboplastin (9035-58-9) ; Sphingomyelin Phosphodiesterase (EC 3.1.4.12) ; Thrombin (EC 3.4.21.5)
Language	English
Publishing date	2019-07-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2019001400
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Article ; Online: Gab2 (Grb2-Associated Binder2) Plays a Crucial Role in Inflammatory Signaling and Endothelial Dysfunction.

Kondreddy, Vijay / Magisetty, Jhansi / Keshava, Shiva / Rao, L Vijaya Mohan / Pendurthi, Usha R

Arteriosclerosis, thrombosis, and vascular biology

2021 Volume 41, Issue 6, Page(s) 1987–2005

Abstract: Figure: see text]. ...

Abstract	[Figure: see text].
MeSH term(s)	Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Cytokines/metabolism ; Disease Models, Animal ; Endotoxins ; Extracellular Traps/metabolism ; Female ; Human Umbilical Vein Endothelial Cells/metabolism ; Human Umbilical Vein Endothelial Cells/pathology ; Humans ; Inflammation/genetics ; Inflammation/metabolism ; Inflammation/pathology ; Inflammation Mediators/metabolism ; Lung/metabolism ; Lung/microbiology ; Lung/pathology ; Male ; Mice, Knockout ; Pneumococcal Infections/genetics ; Pneumococcal Infections/metabolism ; Pneumococcal Infections/microbiology ; Pneumococcal Infections/pathology ; Pneumonia, Bacterial/genetics ; Pneumonia, Bacterial/metabolism ; Pneumonia, Bacterial/microbiology ; Pneumonia, Bacterial/pathology ; Signal Transduction ; Thrombin/metabolism ; Mice
Chemical Substances	Adaptor Proteins, Signal Transducing ; Cytokines ; Endotoxins ; GAB2 protein, human ; Gab2 protein, mouse ; Inflammation Mediators ; endotoxin, Escherichia coli (67924-63-4) ; Thrombin (EC 3.4.21.5)
Language	English
Publishing date	2021-04-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1221433-4
ISSN	1524-4636 ; 1079-5642
ISSN (online)	1524-4636
ISSN	1079-5642
DOI	10.1161/ATVBAHA.121.316153
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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito