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Hemostasis, Thrombosis, and Immunothrombosis
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Hemostasis, Thrombosis, and Immunothrombosis

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (20 October 2023) | Viewed by 11887

Special Issue Editors

Dr. John Kostyak

E-Mail Website
Guest Editor
Cardeza Foundation for Hematologic Research, Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA
Interests: platelets; sepsis; infection; thrombosis; hemostasis
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Ulhas P. Naik

E-Mail Website
Guest Editor
Department of Medicine, Cardeza Center for Hemostasis, Thrombosis, and Vascular Biology, Cardeza Foundation for Hematologic Research, Thomas Jefferson University, Philadelphia, PA 19107, USA
Interests: cell-cell interactions; cell-extracellular matrix interactions; molecular mechanisms of cardiovascular diseases; tumor-induced angiogenesis; adhesion molecules; jam-a; CIB1; platelet activation

Special Issue Information

Dear Colleagues, 

Complications from cardiovascular diseases that lead to myocardial infarction, stroke, and pulmonary embolism are the leading causes of death worldwide, representing 33% of total worldwide deaths. Unfortunately, the mortality from cardiovascular diseases increased between 2010 and 2019. The prime drivers of mortality from cardiovascular diseases are platelets and the coagulation cascade. Moreover, the global pandemic caused by CARS-CoV-2 highlighted the concept of immunothrombosis, whereby microthrombi are formed due to platelet and coagulation cascade activation as a result of inflammation. Similarly, immunothrombosis is integral to the development of thrombotic shock in septic patients. The above conditions all result from a complex interplay between platelets, coagulation, innate immunity, and the endothelium. It is of paramount importance that we enhance our understanding of the mechanisms behind these crucial facets of cardiovascular function in order to design suitable therapeutics. We are most interested in reviews or original reports that delineate the novel mechanisms of pathological thrombosis, physiological hemostasis, or immunothrombosis. Potential topics include, but are not limited to:

  • Platelets in thrombosis or hemostasis;
  • platelet–leukocyte interactions during immune responses;
  • coagulation responses during sepsis;
  • coagulation responses during SARS-CoV-2 infection;
  • platelet function during sepsis;
  • platelet function during SARS-CoV-2 infection;
  • endothelial cell function in systemic inflammation.

Dr. John Kostyak
Prof. Dr. Ulhas P. Naik
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • platelets
  • thrombosis
  • hemostasis
  • immunothrombosis
  • SARS-CoV-2
  • endothelium
  • leukocytes cardiovascular disease

Published Papers (5 papers)

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Review

13 pages, 817 KiB  
Review
The Function of ASK1 in Sepsis and Stress-Induced Disorders
by John C. Kostyak, Steven E. McKenzie and Ulhas P. Naik
Int. J. Mol. Sci. 2024, 25(1), 213; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25010213 - 22 Dec 2023
Viewed by 647
Abstract
Apoptosis signal-regulating kinase 1 (ASK1) is a serine-threonine kinase that is ubiquitously expressed in nucleated cells and is responsible for the activation of multiple mitogen-activated protein kinases (MAPK) to regulate cell stress. Activation of ASK1 via cellular stress leads to activation of downstream [...] Read more.
Apoptosis signal-regulating kinase 1 (ASK1) is a serine-threonine kinase that is ubiquitously expressed in nucleated cells and is responsible for the activation of multiple mitogen-activated protein kinases (MAPK) to regulate cell stress. Activation of ASK1 via cellular stress leads to activation of downstream signaling components, activation of transcription factors, and proinflammatory cytokine production. ASK1 is also expressed in anucleate platelets and is a key player in platelet activation as it is important for signaling. Interestingly, the mechanism of ASK1 activation is cell type-dependent. In this review we will explore how ASK1 regulates a variety of cellular processes from innate immune function to thrombosis and hemostasis. We will discuss how ASK1 influences FcγRIIA-mediated platelet reactivity and how that reactivity drives platelet clearance. Furthermore, we will explore the role of ASK1 in thromboxane (TxA2) generation, which highlights differences in the way ASK1 functions in mouse and human platelets. Full article
(This article belongs to the Special Issue Hemostasis, Thrombosis, and Immunothrombosis)
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28 pages, 10069 KiB  
Review
The Crossroads of the Coagulation System and the Immune System: Interactions and Connections
by Grzegorz Wilhelm, Paulina Mertowska, Sebastian Mertowski, Anna Przysucha, Jerzy Strużyna, Ewelina Grywalska and Kamil Torres
Int. J. Mol. Sci. 2023, 24(16), 12563; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241612563 - 08 Aug 2023
Cited by 3 | Viewed by 3496
Abstract
The coagulation and immune systems, two vital systems in the human body, share intimate connections that fundamentally determine patient health. These systems work together through several common regulatory pathways, including the Tissue Factor (TF) Pathway. Immune cells expressing TF and producing pro-inflammatory cytokines [...] Read more.
The coagulation and immune systems, two vital systems in the human body, share intimate connections that fundamentally determine patient health. These systems work together through several common regulatory pathways, including the Tissue Factor (TF) Pathway. Immune cells expressing TF and producing pro-inflammatory cytokines can influence coagulation, while coagulation factors and processes reciprocally impact immune responses by activating immune cells and controlling their functions. These shared pathways contribute to maintaining health and are also involved in various pathological conditions. Dysregulated coagulation, triggered by infection, inflammation, or tissue damage, can result in conditions such as disseminated intravascular coagulation (DIC). Concurrently, immune dysregulation may lead to coagulation disorders and thrombotic complications. This review elucidates these intricate interactions, emphasizing their roles in the pathogenesis of autoimmune diseases and cancer. Understanding the complex interplay between these systems is critical for disease management and the development of effective treatments. By exploring these common regulatory mechanisms, we can uncover innovative therapeutic strategies targeting these intricate disorders. Thus, this paper presents a comprehensive overview of the mutual interaction between the coagulation and immune systems, highlighting its significance in health maintenance and disease pathology. Full article
(This article belongs to the Special Issue Hemostasis, Thrombosis, and Immunothrombosis)
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Figure 1

13 pages, 1758 KiB  
Review
Species Differences in Platelet Protease-Activated Receptors
by Stephanie A. Renna, Steven E. McKenzie and James V. Michael
Int. J. Mol. Sci. 2023, 24(9), 8298; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24098298 - 05 May 2023
Cited by 1 | Viewed by 1419
Abstract
Protease-activated receptors (PARs) are a class of integral membrane proteins that are cleaved by a variety of proteases, most notably thrombin, to reveal a tethered ligand and promote activation. PARs are critical mediators of platelet function in hemostasis and thrombosis, and therefore are [...] Read more.
Protease-activated receptors (PARs) are a class of integral membrane proteins that are cleaved by a variety of proteases, most notably thrombin, to reveal a tethered ligand and promote activation. PARs are critical mediators of platelet function in hemostasis and thrombosis, and therefore are attractive targets for anti-platelet therapies. Animal models studying platelet PAR physiology have relied heavily on genetically modified mouse strains, which have provided ample insight but have some inherent limitations. The current review aims to summarize the notable PAR expression and functional differences between the mouse and human, in addition to highlighting some recently developed tools to further study human physiology in mouse models. Full article
(This article belongs to the Special Issue Hemostasis, Thrombosis, and Immunothrombosis)
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Figure 1

23 pages, 1692 KiB  
Review
The Signaling Pathway of the ADP Receptor P2Y12 in the Immune System: Recent Discoveries and New Challenges
by Philomena Entsie, Ying Kang, Emmanuel Boadi Amoafo, Torsten Schöneberg and Elisabetta Liverani
Int. J. Mol. Sci. 2023, 24(7), 6709; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24076709 - 04 Apr 2023
Cited by 3 | Viewed by 4187
Abstract
P2Y12 is a G-protein-coupled receptor that is activated upon ADP binding. Considering its well-established role in platelet activation, blocking P2Y12 has been used as a therapeutic strategy for antiplatelet aggregation in cardiovascular disease patients. However, receptor studies have shown that P2Y [...] Read more.
P2Y12 is a G-protein-coupled receptor that is activated upon ADP binding. Considering its well-established role in platelet activation, blocking P2Y12 has been used as a therapeutic strategy for antiplatelet aggregation in cardiovascular disease patients. However, receptor studies have shown that P2Y12 is functionally expressed not only in platelets and the microglia but also in other cells of the immune system, such as in monocytes, dendritic cells, and T lymphocytes. As a result, studies were carried out investigating whether therapies targeting P2Y12 could also ameliorate inflammatory conditions, such as sepsis, rheumatoid arthritis, neuroinflammation, cancer, COVID-19, atherosclerosis, and diabetes-associated inflammation in animal models and human subjects. This review reports what is known about the expression of P2Y12 in the cells of the immune system and the effect of P2Y12 activation and/or inhibition in inflammatory conditions. Lastly, we will discuss the major problems and challenges in studying this receptor and provide insights on how they can be overcome. Full article
(This article belongs to the Special Issue Hemostasis, Thrombosis, and Immunothrombosis)
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13 pages, 1385 KiB  
Review
TULA-Family Regulators of Platelet Activation
by Satya P. Kunapuli and Alexander Y. Tsygankov
Int. J. Mol. Sci. 2022, 23(23), 14910; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232314910 - 28 Nov 2022
Cited by 2 | Viewed by 1286
Abstract
The two members of the UBASH3/TULA/STS-protein family have been shown to critically regulate cellular processes in multiple biological systems. The regulatory function of TULA-2 (also known as UBASH3B or STS-1) in platelets is one of the best examples of the involvement of UBASH3/TULA/STS [...] Read more.
The two members of the UBASH3/TULA/STS-protein family have been shown to critically regulate cellular processes in multiple biological systems. The regulatory function of TULA-2 (also known as UBASH3B or STS-1) in platelets is one of the best examples of the involvement of UBASH3/TULA/STS proteins in cellular regulation. TULA-2 negatively regulates platelet signaling mediated by ITAM- and hemITAM-containing membrane receptors that are dependent on the protein tyrosine kinase Syk, which currently represents the best-known dephosphorylation target of TULA-2. The biological responses of platelets to collagen and other physiological agonists are significantly downregulated as a result. The protein structure, enzymatic activity and regulatory functions of UBASH3/TULA/STS proteins in the context of platelet responses and their regulation are discussed in this review. Full article
(This article belongs to the Special Issue Hemostasis, Thrombosis, and Immunothrombosis)
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