Molecular Mechanisms of Hemostasis, Thrombosis and Thrombo-Inflammation

Article Biochemistry & Molecular Biology

The Platelet Collagen Receptor GPVI Is Cleaved by Tspan15/ADAM10 and Tspan33/ADAM10 Molecular Scissors

Chek Ziu Koo et al.

Summary: The interaction between Tspan15 and GPVI is crucial for the cleavage of GPVI and Tspan15 plays a more important role in this process. The extracellular region of Tspan15 is critical in promoting the cleavage of GPVI.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Review Biochemistry & Molecular Biology

Role of Neutrophils and NETs in Animal Models of Thrombosis

Estelle Carminita et al.

Summary: Thrombosis is a major cause of death worldwide and is linked to cardiovascular diseases, cancer, neutrophils, and neutrophil extracellular traps (NETs). Understanding the cellular and molecular mechanisms of platelet thrombus formation is a significant challenge for scientists.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Biochemistry & Molecular Biology

Role of Tyrosine Kinase Syk in Thrombus Stabilisation at High Shear

Gina Perrella et al.

Summary: The study shows that Syk tyrosine kinase regulates the stability of thrombus under flow conditions, and this process involves pathways additional to activation of GPVI by collagen.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Biochemistry & Molecular Biology

Temporal Roles of Platelet and Coagulation Pathways in Collagen- and Tissue Factor-Induced Thrombus Formation

Stefano Navarro et al.

Summary: This study utilized microfluidics technology and pharmacological intervention to acutely block and investigate key pathways of thrombus and clot formation in a short period of time, revealing the crucial roles of certain molecular pathways in the initial minutes of thrombus buildup.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Biochemistry & Molecular Biology

Structure-Based Cyclic Glycoprotein Ibα-Derived Peptides Interfering with von Willebrand Factor-Binding, Affecting Platelet Aggregation under Shear

Johana Hrdinova et al.

Summary: This study designed and synthesized stable cyclic peptides to interfere with the interaction between VWF A1 domain and GPIb alpha. The selected peptides showed low binding free energy and retained their interference in the binding of VWF to GPIb-V-IX, as confirmed by flow cytometry. These peptides phenotypically mimicked the changes seen with the anti-VWF A1 domain antibody CLB-RAg35, although they were less potent. The improved peptide opt-mono-ORbIT demonstrated increased inhibitory activity under flow.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Biochemistry & Molecular Biology

Heparin-Functionalized Adsorbents Eliminate Central Effectors of Immunothrombosis, including Platelet Factor 4, High-Mobility Group Box 1 Protein and Histones

Marie Ebeyer-Masotta et al.

Summary: Inflammation and thrombosis are closely related in various diseases, including ischemic events, sepsis, and COVID-19. Activated neutrophils, platelets, and other factors drive immunothrombosis. Research has shown that the use of heparin-functionalized adsorbents can effectively remove central effectors of immunothrombosis.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Review Biochemistry & Molecular Biology

Beyond Hemostasis: Platelet Innate Immune Interactions and Thromboinflammation

Jonathan Mandel et al.

Summary: There is growing evidence that platelets have functions beyond their traditional roles in thrombosis and hemostasis. They interact and regulate cells of the innate immune system, such as neutrophils, monocytes, and macrophages, and play roles in inflammatory processes, infection, and cancer. This review focuses on platelet activation in hemostatic and inflammatory processes, as well as platelet interactions with neutrophils and monocytes/macrophages. The contributions of major platelet receptors and secretions from platelet granules on platelet-neutrophil aggregate and neutrophil extracellular trap (NET) formation in various diseases are examined.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Biochemistry & Molecular Biology

Mechanisms Underlying Dichotomous Procoagulant COAT Platelet Generation-A Conceptual Review Summarizing Current Knowledge

Lucas Veuthey et al.

Summary: Procoagulant platelets are key regulators of thrombus formation and derive from cells capable of accumulating enough cytosolic calcium. We lack insight into the actual mechanisms controlling the dichotomous pattern of procoagulant versus aggregating phenotype.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Biochemistry & Molecular Biology

Formation of Neutrophil Extracellular Traps by Reduction of Cellular Cholesterol Is Independent of Oxygen and HIF-1α

Timo Henneck et al.

Summary: This study investigates the effect of oxygen and the oxygen stress regulator HIF-1 alpha on cholesterol-dependent NET formation. The researchers found that the formation of NETs was significantly induced by M beta CD under both normoxic and hypoxic conditions in murine neutrophils and human neutrophils. Similar observations were made in human neutrophils stimulated with M beta CD or statins.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Biochemistry & Molecular Biology

Rac Inhibition Causes Impaired GPVI Signalling in Human Platelets through GPVI Shedding and Reduction in PLCγ2 Phosphorylation

Raluca A. Neagoe et al.

Summary: The study reveals the importance of Rac1 in the activation of human and murine platelets in response to GPVI ligands, although the mode of action differs between the two species.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Biochemistry & Molecular Biology

PCSK9 Induces Tissue Factor Expression by Activation of TLR4/NFkB Signaling

Valentina Scalise et al.

Summary: PCSK9 induces TF expression through activation of the TLR4/NFkB signaling pathway, with TF playing an essential role in both coagulation and inflammation.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Biochemistry & Molecular Biology

Early Adventitial Activation and Proliferation in a Mouse Model of Arteriovenous Stenosis: Opportunities for Intervention

Jenq-Shyong Chan et al.

Summary: In a mouse model of AVF stenosis, early and rapid adventitial proliferation and macrophage infiltration were observed, reaching a peak at 7 days post-surgery. Surprisingly, there was minimal macrophage infiltration or proliferation in the neointimal region at either 7 or 14 days, while endothelial cell proliferation increased rapidly between 2 and 7 days, peaking at 14 days. These findings suggest that adventitial proliferation and macrophage infiltration may play a critical role in the downstream pathways of neointimal hyperplasia and remodeling.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Review Biochemical Research Methods

Multi-omics approaches for revealing the complexity of cardiovascular disease

Stephen Doran et al.

Summary: The development and progression of cardiovascular disease is mainly attributed to factors such as atherosclerosis, thrombosis, cardiac remodelling, and gut microbiota. Understanding the underlying molecular mechanisms and utilizing systems biology approaches are crucial in identifying novel drug targets and biomarkers for CVD treatment strategies. Recent advances in gut microbiota research have shed light on the impact of diet and microbial composition on CVD development.

BRIEFINGS IN BIOINFORMATICS (2021)

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Article Cardiac & Cardiovascular Systems

Inflammation, Infection and Venous Thromboembolism

Meaghan E. Colling et al.

Summary: The association between inflammation, infection, and venous thrombosis is crucial and can lead to pathological thrombosis. Cells like neutrophils, monocytes, and platelets play essential roles in host defense and thrombus formation. Understanding these mechanisms has advanced knowledge in human physiology and pathophysiology, offering new therapeutic targets for the treatment of thrombosis.

CIRCULATION RESEARCH (2021)

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Article Multidisciplinary Sciences

Assessment of a complete and classified platelet proteome from genome-wide transcripts of human platelets and megakaryocytes covering platelet functions

Jingnan Huang et al.

Summary: Novel analysis of platelet and megakaryocyte transcriptome revealed high similarity between their transcriptomes, with redistribution of mRNAs upon platelet shedding from megakaryocytes. A prediction model based on protein function, transcript level and (peri)nuclear localization estimated the achievable proteome of about 10 k proteins, with identification of additional proteins related to thrombosis and platelet disorders. This genome-wide platelet transcriptome provides a valuable resource for studying the roles of unknown platelet proteins in health and disease.

SCIENTIFIC REPORTS (2021)

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Article Biochemistry & Molecular Biology