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Molecular Focus on Venous Thrombosis (DVT/VTE)
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Molecular Focus on Venous Thrombosis (DVT/VTE)

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

Deadline for manuscript submissions: closed (31 August 2020) | Viewed by 39950

Special Issue Editor

Prof. Dr. Alexander Brill

E-Mail Website
Guest Editor
1. Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
2. Department of Pathophysiology, Sechenov First Moscow State Medical University, Moscow, Russia
Interests: thrombosis; vascular biology; cardiovascular diseases; deep vein thrombosis (DVT); stroke
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Venous thromboembolism (VTE), consisting of deep vein thrombosis (DVT) and its major complication, pulmonary embolism (PE), is a serious health issue worldwide. Mechanisms of DVT development are substantially different from arterial thrombosis and remain incompletely understood. In particular, recent studies have demonstrated the pivotal role of different components of the immune system and local inflammatory responses (such as neutrophil extracellular traps or mast cells) in DVT initiation. Research using animal models demonstrates multiple novel molecules that might be useful for venous thrombosis prediction (biomarkers), and targets potentially beneficial for venous thrombosis prevention in clinical setting. Another fundamental and clinical problem is venous thrombus recanalization and resolution, which develops more similarly to the wound healing process than to classic fibrinolysis.

This Special Issue is devoted to a discussion of new insights into mechanisms of DVT initiation, progression, and resolution, as well as contemporary experimental tools used to study these processes. It will include but is not limited to the following subtopics:

  • Animal models of venous thrombosis
  • Mechanisms of venous thrombosis initiation
  • The role of the immune system and inflammation in venous thrombosis
  • Mechanisms of venous thrombosis resolution
  • Classic and emerging novel biomarkers of venous thrombosis and others

This is the conjunct Special Issue both in IJMS and Diagnostics. Authors are free to choose the journal they would like to submit to based on their submission topic.

Prof. Dr. Alexander Brill
Guest Editor

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

  • Venous thromboembolism (VTE)
  • Deep vein thrombosis (DVT)
  • Pulmonary embolism (PE)
  • Thrombus resolution
  • Immune system
  • Inflammatory response
  • Novel molecules
  • Biomarkers
  • New targets

Published Papers (7 papers)

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Editorial

Jump to: Research, Review

3 pages, 159 KiB  
Editorial
Multiple Facets of Venous Thrombosis
by Alexander Brill
Int. J. Mol. Sci. 2021, 22(8), 3853; https://doi.org/10.3390/ijms22083853 - 08 Apr 2021
Cited by 14 | Viewed by 2697
Abstract
Venous thromboembolism, a complex disease combining deep vein thrombosis (DVT) and its most dangerous complication, pulmonary embolism (PE), strikes millions of people worldwide [...] Full article
(This article belongs to the Special Issue Molecular Focus on Venous Thrombosis (DVT/VTE))

Research

Jump to: Editorial, Review

13 pages, 1801 KiB  
Article
Depletion of CD4 and CD8 Positive T Cells Impairs Venous Thrombus Resolution in Mice
by Subhradip Mukhopadhyay, Joel Gabre, Christine Chabasse, Jonathan S. Bromberg, Toni M. Antalis and Rajabrata Sarkar
Int. J. Mol. Sci. 2020, 21(5), 1650; https://doi.org/10.3390/ijms21051650 - 28 Feb 2020
Cited by 9 | Viewed by 3921
Abstract
Resolution of deep venous thrombosis involves coordinated inflammatory processes. T cells regulate inflammation in vivo and modulate vascular remodeling in other settings, but their role in venous thrombus resolution remains undefined. To determine the role of T cells in venous thrombus resolution in [...] Read more.
Resolution of deep venous thrombosis involves coordinated inflammatory processes. T cells regulate inflammation in vivo and modulate vascular remodeling in other settings, but their role in venous thrombus resolution remains undefined. To determine the role of T cells in venous thrombus resolution in vivo, stasis induced thrombi were created by vena cava ligation in outbred CD-1 mice. CD4 and CD8 positive T cells, as determined by flow cytometry, were present in thrombi both during thrombus formation and resolution. Depletion of the CD4 and CD8 positive T cells by antibody treatment selectively impaired thrombus resolution compared to animals treated with isotype control antibodies, without an effect on venous thrombus formation. Quantitation of intra-thrombus macrophage numbers, fibrinolytic marker expression, and gelatinolytic activity by zymography revealed that T cell depletion decreased the number of macrophages, reduced the expression of fibrinolytic marker urokinase plasminogen activator (uPA), and decreased the activity of matrix metalloprotinease-9 (MMP-9). These data implicate CD4 and CD8 positive T cells in functionally contributing to venous thrombus resolution, thus representing a potential therapeutic target, but also underscoring potential risks involved in T cell depletion used clinically for solid organ and hematopoietic transplantation procedures. Full article
(This article belongs to the Special Issue Molecular Focus on Venous Thrombosis (DVT/VTE))
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Review

Jump to: Editorial, Research

20 pages, 688 KiB  
Review
Sickle Cell Disease: A Paradigm for Venous Thrombosis Pathophysiology
by Maria A. Lizarralde-Iragorri and Arun S. Shet
Int. J. Mol. Sci. 2020, 21(15), 5279; https://doi.org/10.3390/ijms21155279 - 25 Jul 2020
Cited by 21 | Viewed by 8014
Abstract
Venous thromboembolism (VTE) is an important cause of vascular morbidity and mortality. Many risk factors have been identified for venous thrombosis that lead to alterations in blood flow, activate the vascular endothelium, and increase the propensity for blood coagulation. However, the precise molecular [...] Read more.
Venous thromboembolism (VTE) is an important cause of vascular morbidity and mortality. Many risk factors have been identified for venous thrombosis that lead to alterations in blood flow, activate the vascular endothelium, and increase the propensity for blood coagulation. However, the precise molecular and cellular mechanisms that cause blood clots in the venous vasculature have not been fully elucidated. Patients with sickle cell disease (SCD) demonstrate all the risk factors for venous stasis, activated endothelium, and blood hypercoagulability, making them particularly vulnerable to VTE. In this review, we will discuss how mouse models have elucidated the complex vascular pathobiology of SCD. We review the dysregulated pathways of inflammation and coagulation in SCD and how the resultant hypercoagulable state can potentiate thrombosis through down-regulation of vascular anticoagulants. Studies of VTE pathogenesis using SCD mouse models may provide insight into the intersection between the cellular and molecular processes involving inflammation and coagulation and help to identify novel mechanistic pathways. Full article
(This article belongs to the Special Issue Molecular Focus on Venous Thrombosis (DVT/VTE))
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18 pages, 909 KiB  
Review
Pulmonary Artery Thrombosis: A Diagnosis That Strives for Its Independence
by Olga Porembskaya, Yana Toropova, Vladimir Tomson, Kirill Lobastov, Leonid Laberko, Viacheslav Kravchuk, Sergey Saiganov and Alexander Brill
Int. J. Mol. Sci. 2020, 21(14), 5086; https://doi.org/10.3390/ijms21145086 - 18 Jul 2020
Cited by 22 | Viewed by 5544
Abstract
According to a widespread theory, thrombotic masses are not formed in the pulmonary artery (PA) but result from migration of blood clots from the venous system. This concept has prevailed in clinical practice for more than a century. However, a new technologic era [...] Read more.
According to a widespread theory, thrombotic masses are not formed in the pulmonary artery (PA) but result from migration of blood clots from the venous system. This concept has prevailed in clinical practice for more than a century. However, a new technologic era has brought forth more diagnostic possibilities, and it has been shown that thrombotic masses in the PA could, in many cases, be found without any obvious source of emboli. Chronic obstructive pulmonary disease, asthma, sickle cell anemia, emergency and elective surgery, viral pneumonia, and other conditions could be complicated by PA thrombosis development without concomitant deep vein thrombosis (DVT). Different pathologies have different causes for local PA thrombotic process. As evidenced by experimental results and clinical observations, endothelial and platelet activation are the crucial mechanisms of this process. Endothelial dysfunction can impair antithrombotic function of the arterial wall through downregulation of endothelial nitric oxide synthase (eNOS) or via stimulation of adhesion receptor expression. Hypoxia, proinflammatory cytokines, or genetic mutations may underlie the procoagulant phenotype of the PA endothelium. Both endotheliocytes and platelets could be activated by protease mediated receptor (PAR)- and receptors for advanced glycation end (RAGE)-dependent mechanisms. Hypoxia, in particular induced by high altitudes, could play a role in thrombotic complications as a trigger of platelet activity. In this review, we discuss potential mechanisms of PA thrombosis in situ. Full article
(This article belongs to the Special Issue Molecular Focus on Venous Thrombosis (DVT/VTE))
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Graphical abstract

24 pages, 1720 KiB  
Review
Resolution of Deep Venous Thrombosis: Proposed Immune Paradigms
by J. Matthew Nicklas, Aviva E. Gordon and Peter K. Henke
Int. J. Mol. Sci. 2020, 21(6), 2080; https://doi.org/10.3390/ijms21062080 - 18 Mar 2020
Cited by 40 | Viewed by 8646
Abstract
Venous thromboembolism (VTE) is a pathology encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE) associated with high morbidity and mortality. Because patients often present after a thrombus has already formed, the mechanisms that drive DVT resolution are being investigated in search of [...] Read more.
Venous thromboembolism (VTE) is a pathology encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE) associated with high morbidity and mortality. Because patients often present after a thrombus has already formed, the mechanisms that drive DVT resolution are being investigated in search of treatment. Herein, we review the current literature, including the molecular mechanisms of fibrinolysis and collagenolysis, as well as the critical cellular roles of macrophages, neutrophils, and endothelial cells. We propose two general models for the operation of the immune system in the context of venous thrombosis. In early thrombus resolution, neutrophil influx stabilizes the tissue through NETosis. Meanwhile, macrophages and intact neutrophils recognize the extracellular DNA by the TLR9 receptor and induce fibrosis, a complimentary stabilization method. At later stages of resolution, pro-inflammatory macrophages police the thrombus for pathogens, a role supported by both T-cells and mast cells. Once they verify sterility, these macrophages transform into their pro-resolving phenotype. Endothelial cells both coat the stabilized thrombus, a necessary early step, and can undergo an endothelial-mesenchymal transition, which impedes DVT resolution. Several of these interactions hold promise for future therapy. Full article
(This article belongs to the Special Issue Molecular Focus on Venous Thrombosis (DVT/VTE))
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Graphical abstract

18 pages, 577 KiB  
Review
From Classical Laboratory Parameters to Novel Biomarkers for the Diagnosis of Venous Thrombosis
by Larisa Anghel, Radu Sascău, Rodica Radu and Cristian Stătescu
Int. J. Mol. Sci. 2020, 21(6), 1920; https://doi.org/10.3390/ijms21061920 - 11 Mar 2020
Cited by 24 | Viewed by 4451
Abstract
Venous thrombosis is a common and potentially fatal disease, because of its high morbidity and mortality, especially in hospitalized patients. To establish the diagnosis of venous thrombosis, in the last years, a multi-modality approach that involves not only imaging modalities but also serology [...] Read more.
Venous thrombosis is a common and potentially fatal disease, because of its high morbidity and mortality, especially in hospitalized patients. To establish the diagnosis of venous thrombosis, in the last years, a multi-modality approach that involves not only imaging modalities but also serology has been evolving. Multiple studies have demonstrated the use of some biomarkers, such as D-dimer, selectins, microparticles or inflammatory cytokines, for the diagnosis and treatment of venous thrombosis, but there is no single biomarker available to exclusively confirm the diagnosis of venous thrombosis. Considering the fact that there are some issues surrounding the management of patients with venous thrombosis and the duration of treatment, recent studies support the idea that these biomarkers may help guide the length of appropriate anticoagulation treatment, by identifying patients at high risk of recurrence. At the same time, biomarkers may help predict thrombus evolution, potentially identifying patients that would benefit from more aggressive therapies. This review focuses on classic and novel biomarkers currently under investigation, discussing their diagnostic performance and potential benefit in guiding the therapy for venous thrombosis. Full article
(This article belongs to the Special Issue Molecular Focus on Venous Thrombosis (DVT/VTE))
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27 pages, 2043 KiB  
Review
Reactive Oxygen Species in Venous Thrombosis
by Clemens Gutmann, Richard Siow, Adam M. Gwozdz, Prakash Saha and Alberto Smith
Int. J. Mol. Sci. 2020, 21(6), 1918; https://doi.org/10.3390/ijms21061918 - 11 Mar 2020
Cited by 63 | Viewed by 5889
Abstract
Reactive oxygen species (ROS) have physiological roles as second messengers, but can also exert detrimental modifications on DNA, proteins and lipids if resulting from enhanced generation or reduced antioxidant defense (oxidative stress). Venous thrombus (DVT) formation and resolution are influenced by ROS through [...] Read more.
Reactive oxygen species (ROS) have physiological roles as second messengers, but can also exert detrimental modifications on DNA, proteins and lipids if resulting from enhanced generation or reduced antioxidant defense (oxidative stress). Venous thrombus (DVT) formation and resolution are influenced by ROS through modulation of the coagulation, fibrinolysis, proteolysis and the complement system, as well as the regulation of effector cells such as platelets, endothelial cells, erythrocytes, neutrophils, mast cells, monocytes and fibroblasts. Many conditions that carry an elevated risk of venous thrombosis, such as the Antiphospholipid Syndrome, have alterations in their redox homeostasis. Dietary and pharmacological antioxidants can modulate several important processes involved in DVT formation, but their overall effect is unknown and there are no recommendations regarding their use. The development of novel antioxidant treatments that aim to abrogate the formation of DVT or promote its resolution will depend on the identification of targets that enable ROS modulation confined to their site of interest in order to prevent off-target effects on physiological redox mechanisms. Subgroups of patients with increased systemic oxidative stress might benefit from unspecific antioxidant treatment, but more clinical studies are needed to bring clarity to this issue. Full article
(This article belongs to the Special Issue Molecular Focus on Venous Thrombosis (DVT/VTE))
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