Contractility defects hinder glycoprotein VI-mediated platelet activation and affect platelet functions beyond clot contraction
CONCLUSION: Our findings highlight the importance of both active contractile and passive crosslinking roles of myosin IIA in the platelet cytoskeleton. They support the hypothesis that highly contractile platelets are needed for hemostasis and further suggest a supportive role for myosin IIA in GPVI signaling.PMID:38379711 | PMC:PMC10877441 | DOI:10.1016/j.rpth.2024.102322 (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - February 21, 2024 Category: Hematology Authors: Martin Kenny Alice Y Pollitt Smita Patil Dishon W Hiebner Albert Smolenski Natalija Lakic Robert Fisher Reema Alsufyani Sebastian Lickert Viola Vogel Ingmar Schoen Source Type: research
Coronary microthrombi in the failing human heart: the role of von Willebrand factor and PECAM-1
Mol Cell Biochem. 2024 Feb 21. doi: 10.1007/s11010-024-04942-0. Online ahead of print.ABSTRACTThe recognition of microthrombi in the heart microcirculation has recently emerged from studies in COVID-19 decedents. The present study investigated the ultrastructure of coronary microthrombi in heart failure (HF) due to cardiomyopathies that are unrelated to COVID-19 infection. In addition, we have investigated the role of von Willebrand factor (VWF) and PECAM-1 in microthrombus formation. We used electron microscopy to investigate the occurrence of microthrombi in patients with HF due to dilated (DCM, n = 7), inflammatory (MYO...
Source: Molecular and Cellular Biochemistry - February 21, 2024 Category: Biochemistry Authors: Sawa Kostin Theodoros Giannakopoulos Manfred Richter Florian Krizanic Benjamin Sasko Oliver Ritter Nikolaos Pagonas Source Type: research
Molecular Interactions Required for Activation of Complement Component C2 Include Exosites Located on the Serine Protease Domain of C1s and Mannose-Binding Lectin Associated Protease-2
In this study, we have shown that the ABE on the SP of both C1s and MASP-2 is crucial for efficient cleavage of C2, with mutant forms of the proteases greatly impaired in their rate of cleavage of C2. We have additionally shown that the site of binding for the ABE of the proteases is very likely to be located on the von Willebrand factor domain of C2, with the precise area differing between the enzymes: whereas C1s requires two anionic clusters on the von Willebrand factor domain to enact efficient cleavage of C2, MASP-2 apparently only requires one. These data provide (to our knowledge) new information about the molecular...
Source: Journal of Immunology - February 19, 2024 Category: Allergy & Immunology Authors: Lilian Hor Jing Pan Robert N Pike Lakshmi C Wijeyewickrema Source Type: research
Integrin α9β1 deficiency does not impact the development of atherosclerosis in mice
Heliyon. 2024 Feb 9;10(4):e25760. doi: 10.1016/j.heliyon.2024.e25760. eCollection 2024 Feb 29.ABSTRACTSushi, von Willebrand factor type A, EGF and pentraxin domain containing 1 (SVEP1) is an extracellular matrix protein that causally promotes cardiovascular disease in humans and mice. However, the receptor mediating the effect of SVEP1 on the development of disease remains unclear. We previously demonstrated that depleting either vascular smooth muscle cell (VSMC)- or myeloid cell-derived integrin α9β1, the first receptor that was identified to interact with SVEP1, did not phenocopy the disease-abrogating effect of deple...
Source: Atherosclerosis - February 19, 2024 Category: Cardiology Authors: In-Hyuk Jung Nathan O Stitziel Source Type: research
Hemophagocytic lymphohistiocytosis is associated with deficiency and closed conformation of ADAMTS-13
CONCLUSION: Our study reported that ADAMTS-13 conformation is closed in HLH and provides an indirect proof that plasmin is not able to massively degrade ADAMTS-13. Further studies on glycosylation and citrullination profiles of ADAMTS-13 are needed to understand their role in HLH.PMID:38371335 | PMC:PMC10869956 | DOI:10.1016/j.rpth.2023.102292 (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - February 19, 2024 Category: Hematology Authors: Am élie Launois Sandrine Valade Eric Mariotte Lionel Galicier Elie Azoulay Elien Roose Karen Vanhoorelbeke Agn ès Veyradier B érangère S Joly Source Type: research
Molecular Interactions Required for Activation of Complement Component C2 Include Exosites Located on the Serine Protease Domain of C1s and Mannose-Binding Lectin Associated Protease-2
In this study, we have shown that the ABE on the SP of both C1s and MASP-2 is crucial for efficient cleavage of C2, with mutant forms of the proteases greatly impaired in their rate of cleavage of C2. We have additionally shown that the site of binding for the ABE of the proteases is very likely to be located on the von Willebrand factor domain of C2, with the precise area differing between the enzymes: whereas C1s requires two anionic clusters on the von Willebrand factor domain to enact efficient cleavage of C2, MASP-2 apparently only requires one. These data provide (to our knowledge) new information about the molecular...
Source: Journal of Immunology - February 19, 2024 Category: Allergy & Immunology Authors: Lilian Hor Jing Pan Robert N Pike Lakshmi C Wijeyewickrema Source Type: research
Integrin α9β1 deficiency does not impact the development of atherosclerosis in mice
Heliyon. 2024 Feb 9;10(4):e25760. doi: 10.1016/j.heliyon.2024.e25760. eCollection 2024 Feb 29.ABSTRACTSushi, von Willebrand factor type A, EGF and pentraxin domain containing 1 (SVEP1) is an extracellular matrix protein that causally promotes cardiovascular disease in humans and mice. However, the receptor mediating the effect of SVEP1 on the development of disease remains unclear. We previously demonstrated that depleting either vascular smooth muscle cell (VSMC)- or myeloid cell-derived integrin α9β1, the first receptor that was identified to interact with SVEP1, did not phenocopy the disease-abrogating effect of deple...
Source: Atherosclerosis - February 19, 2024 Category: Cardiology Authors: In-Hyuk Jung Nathan O Stitziel Source Type: research
Hemophagocytic lymphohistiocytosis is associated with deficiency and closed conformation of ADAMTS-13
CONCLUSION: Our study reported that ADAMTS-13 conformation is closed in HLH and provides an indirect proof that plasmin is not able to massively degrade ADAMTS-13. Further studies on glycosylation and citrullination profiles of ADAMTS-13 are needed to understand their role in HLH.PMID:38371335 | PMC:PMC10869956 | DOI:10.1016/j.rpth.2023.102292 (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - February 19, 2024 Category: Hematology Authors: Am élie Launois Sandrine Valade Eric Mariotte Lionel Galicier Elie Azoulay Elien Roose Karen Vanhoorelbeke Agn ès Veyradier B érangère S Joly Source Type: research
Hemophagocytic lymphohistiocytosis is associated with deficiency and closed conformation of ADAMTS-13
CONCLUSION: Our study reported that ADAMTS-13 conformation is closed in HLH and provides an indirect proof that plasmin is not able to massively degrade ADAMTS-13. Further studies on glycosylation and citrullination profiles of ADAMTS-13 are needed to understand their role in HLH.PMID:38371335 | PMC:PMC10869956 | DOI:10.1016/j.rpth.2023.102292 (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - February 19, 2024 Category: Hematology Authors: Am élie Launois Sandrine Valade Eric Mariotte Lionel Galicier Elie Azoulay Elien Roose Karen Vanhoorelbeke Agn ès Veyradier B érangère S Joly Source Type: research
Case report: Peri-procedural hydroxyurea helps minimize bleeding in patients with Essential Thrombocythemia associated with acquired von Willebrand syndrome
CONCLUSION: Patients with extreme thrombocytosis are at high risk of bleeding due to acquired Von Willebrand Syndrome. Initiation of hydroxyurea at the time of bone marrow exam helps to control platelet count and minimizes the risk of peri-procedural hemorrhage in high-risk Essential Thrombocythemia patients with suspected acquired Von Willebrand Syndrome.PMID:38361779 | PMC:PMC10867169 | DOI:10.3389/fonc.2024.1326209 (Source: Cancer Control)
Source: Cancer Control - February 16, 2024 Category: Cancer & Oncology Authors: Leah Kogan Russell Price Rouslan Kotchetkov Source Type: research
Similar construction of spicules and shell plates: Implications for the origin of chiton biomineralization
In this study, we try to understand the types and diversity of matrix proteins in the biomineralization of chiton shell plates and spicules. Through a comparative analysis, we seek insights into the core biomineralization toolkit of ancestral mollusks. To achieve this, we conducted LC-MS/MS and RT-qPCR analyses to identify the types and relative expression levels of matrix proteins in both shell plates and spicules. The analysis revealed 96 matrix proteins in the spicules. A comparison of biomineralization-related matrix proteins in shell plates and spicules from the same species revealed shared proteins including many unk...
Source: Journal of Proteomics - February 16, 2024 Category: Biochemistry Authors: Haipeng Liu Chuang Liu Wenjing Zhang Yang Yuan Zhenglu Wang Jingliang Huang Source Type: research
Similar construction of spicules and shell plates: Implications for the origin of chiton biomineralization
In this study, we try to understand the types and diversity of matrix proteins in the biomineralization of chiton shell plates and spicules. Through a comparative analysis, we seek insights into the core biomineralization toolkit of ancestral mollusks. To achieve this, we conducted LC-MS/MS and RT-qPCR analyses to identify the types and relative expression levels of matrix proteins in both shell plates and spicules. The analysis revealed 96 matrix proteins in the spicules. A comparison of biomineralization-related matrix proteins in shell plates and spicules from the same species revealed shared proteins including many unk...
Source: Journal of Proteomics - February 16, 2024 Category: Biochemistry Authors: Haipeng Liu Chuang Liu Wenjing Zhang Yang Yuan Zhenglu Wang Jingliang Huang Source Type: research
Clusterin knockdown has effects on intracellular and secreted von Willebrand factor in human umbilical vein endothelial cells
by Allaura A. Cox, Alice Liu, Christopher J. Ng
Alterations in von Willebrand factor (VWF) have an important role in human health and disease. Deficiency of VWF is associated with symptoms of bleeding and excesses of VWF are associated with thrombotic outcomes. Understanding the mechanisms that drive VWF regulation can lead to a better understa nding of modulation of VWF levels in humans. We identified clusterin (CLU) as a potential candidate regulator of VWF based on a single cell RNA sequencing (scRNA-seq) analysis in control endothelial cells (ECs) and von Willebrand disease (VWD) endothelial colony-forming-cells (ECFC...
Source: PLoS One - February 16, 2024 Category: Biomedical Science Authors: Allaura A. Cox Source Type: research
Efanesoctocog alfa: the renaissance of Factor VIII replacement therapy
Haematologica. 2024 Feb 15. doi: 10.3324/haematol.2023.284498. Online ahead of print.ABSTRACTEfanesoctocog alfa (ALTUVIIIOTM, Sanofi-SOBI) is a B domain-deleted single-chain Factor VIII (FVIII) connected to D'D3 domain of von Willebrand Factor (VWF). Its ingenious design allows efanesoctocog alfa to operate independently of endogenous VWF and results in an outstanding 3-4 times longer half-life compared to standard and extended half-life (EHL) FVIII products. The prolonged half-life ensures sustained high levels of factor activity, maintaining normal to near-normal ranges for the majority of the week, facilitating the conv...
Source: Haematologica - February 15, 2024 Category: Hematology Authors: Yesim Dargaud Alexandre Leuci Alejandra Reyes Ruiz Sebastien Lacroix-Desmazes Source Type: research
Mechanism underlying severe deficiency of plasma ADAMTS13 activity in immune thrombotic thrombocytopenic purpura
CONCLUSIONS: We conclude that severe deficiency of plasma ADAMTS13 activity is primarily resulted from antibody-mediated inhibition but the accelerated clearance of plasma ADAMTS13 antigen via immune complexes may also contribute significantly to severe deficiency of plasma ADAMTS13 activity in a subset of patients with acute iTTP.PMID:38360215 | DOI:10.1016/j.jtha.2024.02.003 (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - February 15, 2024 Category: Hematology Authors: X Long Zheng Source Type: research
