Involvement of peptidylarginine deiminase 4 in eosinophil extracellular trap formation and contribution to citrullinated histone signal in thrombi
CONCLUSIONS: As in NETosis, PAD4 can catalyze the formation of EETs. Inhibition of PAD4 decreases EET formation, supporting the future utility of PAD4 inhibitors as possible antithrombotic agents.PMID:38395360 | DOI:10.1016/j.jtha.2024.02.010 (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - February 23, 2024 Category: Hematology Authors: Kimberly Martinod Frederik Denorme Severien Meyers Marilena Crescente Stijn Van Bruggen Mathias Stroobants Patrick M Siegel Ramesh Grandhi Katharina Glatz Thilo Witsch Source Type: research

A noncanonical splicing variant c.875-5  T  & gt;  G in von Willebrand factor causes in-frame exon skipping and type 2A von Willebrand disease
CONCLUSIONS: The VWF splicing site variant (c.875-5 T > G) causes propeptide truncation, severely compromising VWF multimer assembly and tubular storage.PMID:38387303 | DOI:10.1016/j.thromres.2024.02.002 (Source: Cell Research)
Source: Cell Research - February 22, 2024 Category: Cytology Authors: Qian Liang Ziqi Zhang Biying Ding Yanyan Shao Qiulan Ding Jing Dai Xiaobo Hu Wenman Wu Xuefeng Wang Source Type: research

VWD domain stabilization by autocatalytic Asp ‐Pro cleavage
In this study, we investigated the structural and biophysical consequences of Asp-Pro peptide cleavage in a representative FCGBP VWD domain. We found that endogenous Asp-Pro cleavage increases the resistance of the domain to exogenous proteolytic degradation. Tertiary structural interactions made by the newly generated chain termini, as revealed by a crystal structure of an FCGBP segment containing the VWD domain, may explain this observation. Notably, the Gly-Asp peptide bond, upstream of the cleavage site, assumed thecis configuration in the structure. In addition to these local features of the cleavage site, a global or...
Source: Protein Science - February 21, 2024 Category: Biochemistry Authors: Noa Yeshaya, Prashant Kumar Gupta, Orly Dym, David Morgenstern, Dan Thomas Major, Deborah Fass Tags: RESEARCH ARTICLE 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

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