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Special Issue "Molecular and Cellular Basis of Thrombotic Diseases"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 December 2019).

Special Issue Editors

Dr. Oury Cécile
E-Mail Website
Guest Editor
Laboratory of Thrombosis and Hemostasis and Valvular Heart Disease, GIGA‐Cardiovascular Sciences, Department of Cardiology, University of Liège, CHU Sart‐Tilman Liège, Belgium
Interests: platelets; P2 receptors; ITAM receptors; signal transduction; platelet-neutrophil interactions; bacterial infection; inflammation; inflammation-associated cancer; mouse models; intravital microscopy; vascular integrity; thrombosis; valvular heart disease; aortic stenosis; prosthetic heart valves; transcatheter aortic valve implantation
Dr. Sandrine Horman
E-Mail Website
Guest Editor
Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium
Interests: platelets; metabolism; AMPK signaling; thrombosis; myocardial infarction; ventricular remodeling; fibrosis; cardiac fibroblast biology; endothelial barrier; stent; mouse models; translational research

Special Issue Information

Dear Colleagues,

Circulating platelets and coagulation play a crucial role in hemostasis, acting to maintain the integrity of a closed circulatory system after blood vessel injury. Under physiological conditions, regulatory mechanisms restrain thrombus formation. When pathologic processes disturb these mechanisms, thrombosis can occur either in the arterial or in the venous circulation with tremendous impact on human health. Thrombosis is the cause of ischemic heart disease, ischemic stroke, and venous thromboembolism, which account for one in four deaths worldwide.

Current antithrombotic therapy includes antiplatelet and anticoagulant drugs, preventing clot from forming and growing. However, these drugs have adverse side effects, most notably the increased risk of bleeding, and there remains a considerable incidence of thrombosis in patients receiving currently available therapy. There is an unmet medical need for novel antithrombotic agents or strategies with a more favorable safety profile, and better efficacy in certain high-risk patients. It is likely that a broader, more personalized and improved implementation of preventive measures will reduce the disease burden.

The discovery of novel cellular and molecular targets is the matter of intense ongoing research. This Special Issue is dedicated to the description of pathological cellular and molecular mechanisms underlying hemostatic imbalance and thrombosis, the identification of fundamental basis of disease, and the development of molecular interventions to prevent or treat them towards a molecular medicine perspective.

Dr. Oury Cécile
Dr. Sandrine Horman
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 papers will be 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
  • leukocytes
  • coagulation
  • fibrinolysis
  • vascular integrity
  • thrombosis
  • molecular pathology
  • risk factors

Published Papers (7 papers)

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Research

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Open AccessArticle
Role of Platelet Glycoprotein VI and Tyrosine Kinase Syk in Thrombus Formation on Collagen-Like Surfaces
Int. J. Mol. Sci. 2019, 20(11), 2788; https://doi.org/10.3390/ijms20112788 - 07 Jun 2019
Abstract
Platelet interaction with collagens, via von Willebrand factor, is a potent trigger of shear-dependent thrombus formation mediated by subsequent engagement of the signaling collagen receptor glycoprotein (GP)VI, enforced by integrin α2β1. Protein tyrosine kinase Syk is central in the [...] Read more.
Platelet interaction with collagens, via von Willebrand factor, is a potent trigger of shear-dependent thrombus formation mediated by subsequent engagement of the signaling collagen receptor glycoprotein (GP)VI, enforced by integrin α2β1. Protein tyrosine kinase Syk is central in the GPVI-induced signaling pathway, leading to elevated cytosolic Ca2+. We aimed to determine the Syk-mediated thrombogenic activity of several collagen peptides and (fibrillar) type I and III collagens. High-shear perfusion of blood over microspots of these substances resulted in thrombus formation, which was assessed by eight parameters and was indicative of platelet adhesion, activation, aggregation, and contraction, which were affected by the Syk inhibitor PRT-060318. In platelet suspensions, only collagen peptides containing the consensus GPVI-activating sequence (GPO)n and Horm-type collagen evoked Syk-dependent Ca2+ rises. In whole blood under flow, Syk inhibition suppressed platelet activation and aggregation parameters for the collagen peptides with or without a (GPO)n sequence and for all of the collagens. Prediction models based on a regression analysis indicated a mixed role of GPVI in thrombus formation on fibrillar collagens, which was abolished by Syk inhibition. Together, these findings indicate that GPVI-dependent signaling through Syk supports platelet activation in thrombus formation on collagen-like structures regardless of the presence of a (GPO)n sequence. Full article
(This article belongs to the Special Issue Molecular and Cellular Basis of Thrombotic Diseases)
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Review

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Open AccessReview
Platelet Biochemistry and Morphology after Cryopreservation
Int. J. Mol. Sci. 2020, 21(3), 935; https://doi.org/10.3390/ijms21030935 - 31 Jan 2020
Abstract
Platelet cryopreservation has been investigated for several decades as an alternative to room temperature storage of platelet concentrates. The use of dimethylsulfoxide as a cryoprotectant has improved platelet storage and cryopreserved concentrates can be kept at −80 °C for two years. Cryopreserved platelets [...] Read more.
Platelet cryopreservation has been investigated for several decades as an alternative to room temperature storage of platelet concentrates. The use of dimethylsulfoxide as a cryoprotectant has improved platelet storage and cryopreserved concentrates can be kept at −80 °C for two years. Cryopreserved platelets can serve as emergency backup to support stock crises or to disburden difficult logistic areas like rural or military regions. Cryopreservation significantly influences platelet morphology, decreases platelet activation and severely abrogates platelet aggregation. Recent data indicate that cryopreserved platelets have a procoagulant phenotype because thrombin and fibrin formation kicks in earlier compared to room temperature stored platelets. This happens both in static and hydrodynamic conditions. In a clinical setting, low 1-h post transfusion recoveries of cryopreserved platelets represent fast clearance from circulation which may be explained by changes to the platelet GPIbα receptor. Cryopreservation splits the concentrate in two platelet subpopulations depending on GPIbα expression levels. Further research is needed to unravel its physiological importance. Proving clinical efficacy of cryopreserved platelets is difficult because of the heterogeneity of indications and the ambiguity of outcome measures. The procoagulant character of cryopreserved platelets has increased interest for use in trauma stressing the need for double-blinded randomized clinical trials in actively bleeding patients. Full article
(This article belongs to the Special Issue Molecular and Cellular Basis of Thrombotic Diseases)
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Open AccessReview
Coagulatory Defects in Type-1 and Type-2 Diabetes
Int. J. Mol. Sci. 2019, 20(24), 6345; https://doi.org/10.3390/ijms20246345 - 16 Dec 2019
Abstract
Diabetes (both type-1 and type-2) affects millions of individuals worldwide. A major cause of death for individuals with diabetes is cardiovascular diseases, in part since both types of diabetes lead to physiological changes that affect haemostasis. Those changes include altered concentrations of coagulatory [...] Read more.
Diabetes (both type-1 and type-2) affects millions of individuals worldwide. A major cause of death for individuals with diabetes is cardiovascular diseases, in part since both types of diabetes lead to physiological changes that affect haemostasis. Those changes include altered concentrations of coagulatory proteins, hyper-activation of platelets, changes in metal ion homeostasis, alterations in lipid metabolism (leading to lipotoxicity in the heart and atherosclerosis), the presence of pro-coagulatory microparticles and endothelial dysfunction. In this review, we explore the different mechanisms by which diabetes leads to an increased risk of developing coagulatory disorders and how this differs between type-1 and type-2 diabetes. Full article
(This article belongs to the Special Issue Molecular and Cellular Basis of Thrombotic Diseases)
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Open AccessReview
Zinc Homeostasis in Platelet-Related Diseases
Int. J. Mol. Sci. 2019, 20(21), 5258; https://doi.org/10.3390/ijms20215258 - 23 Oct 2019
Abstract
Zn2+ deficiency in the human population is frequent in underdeveloped countries. Worldwide, approximatively 2 billion people consume Zn2+-deficient diets, accounting for 1–4% of deaths each year, mainly in infants with a compromised immune system. Depending on the severity of Zn [...] Read more.
Zn2+ deficiency in the human population is frequent in underdeveloped countries. Worldwide, approximatively 2 billion people consume Zn2+-deficient diets, accounting for 1–4% of deaths each year, mainly in infants with a compromised immune system. Depending on the severity of Zn2+ deficiency, clinical symptoms are associated with impaired wound healing, alopecia, diarrhea, poor growth, dysfunction of the immune and nervous system with congenital abnormalities and bleeding disorders. Poor nutritional Zn2+ status in patients with metastatic squamous cell carcinoma or with advanced non-Hodgkin lymphoma, was accompanied by cutaneous bleeding and platelet dysfunction. Forcing Zn2+ uptake in the gut using different nutritional supplementation of Zn2+ could ameliorate many of these pathological symptoms in humans. Feeding adult rodents with a low Zn2+ diet caused poor platelet aggregation and increased bleeding tendency, thereby attracting great scientific interest in investigating the role of Zn2+ in hemostasis. Storage protein metallothionein maintains or releases Zn2+ in the cytoplasm, and the dynamic change of this cytoplasmic Zn2+ pool is regulated by the redox status of the cell. An increase of labile Zn2+ pool can be toxic for the cells, and therefore cytoplasmic Zn2+ levels are tightly regulated by several Zn2+ transporters located on the cell surface and also on the intracellular membrane of Zn2+ storage organelles, such as secretory vesicles, endoplasmic reticulum or Golgi apparatus. Although Zn2+ is a critical cofactor for more than 2000 transcription factors and 300 enzymes, regulating cell differentiation, proliferation, and basic metabolic functions of the cells, the molecular mechanisms of Zn2+ transport and the physiological role of Zn2+ store in megakaryocyte and platelet function remain elusive. In this review, we summarize the contribution of extracellular or intracellular Zn2+ to megakaryocyte and platelet function and discuss the consequences of dysregulated Zn2+ homeostasis in platelet-related diseases by focusing on thrombosis, ischemic stroke and storage pool diseases. Full article
(This article belongs to the Special Issue Molecular and Cellular Basis of Thrombotic Diseases)
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Open AccessReview
Effects of Estrogens on Platelets and Megakaryocytes
Int. J. Mol. Sci. 2019, 20(12), 3111; https://doi.org/10.3390/ijms20123111 - 25 Jun 2019
Abstract
In women, oral menopausal hormonal therapy (MHT) is associated with adverse effects including an increased incidence of thromboembolic events, classically attributed to an increase in several liver-derived coagulation factors due to hepatic first pass. While platelets are central players in thrombus constitution, their [...] Read more.
In women, oral menopausal hormonal therapy (MHT) is associated with adverse effects including an increased incidence of thromboembolic events, classically attributed to an increase in several liver-derived coagulation factors due to hepatic first pass. While platelets are central players in thrombus constitution, their implication in women treated with estrogens remains incompletely characterized. Platelets and their medullar progenitors, megakaryocytes, express estrogen receptors (ER) that may explain, at least in part, a sensitivity to hormonal changes. The purpose of this review is to summarize our current knowledge of estrogen actions on platelets and megakaryocytes in mice following in vivo administration and in women using MHT. Full article
(This article belongs to the Special Issue Molecular and Cellular Basis of Thrombotic Diseases)
Open AccessReview
Biology and Role of Extracellular Vesicles (EVs) in the Pathogenesis of Thrombosis
Int. J. Mol. Sci. 2019, 20(11), 2840; https://doi.org/10.3390/ijms20112840 - 11 Jun 2019
Cited by 4
Abstract
Extracellular vesicles (EVs) are well-established mediators of cell-to-cell communication. EVs can be released by every cell type and they can be classified into three major groups according to their biogenesis, dimension, density, and predominant protein markers: exosomes, microvesicles, and apoptotic bodies. During their [...] Read more.
Extracellular vesicles (EVs) are well-established mediators of cell-to-cell communication. EVs can be released by every cell type and they can be classified into three major groups according to their biogenesis, dimension, density, and predominant protein markers: exosomes, microvesicles, and apoptotic bodies. During their formation, EVs associate with specific cargo from their parental cell that can include RNAs, free fatty acids, surface receptors, and proteins. The biological function of EVs is to maintain cellular and tissue homeostasis by transferring critical biological cargos to distal or neighboring recipient cells. On the other hand, their role in intercellular communication may also contribute to the pathogenesis of several diseases, including thrombosis. More recently, their physiological and biochemical properties have suggested their use as a therapeutic tool in tissue regeneration as well as a novel option for drug delivery. In this review, we will summarize the impact of EVs released from blood and vascular cells in arterial and venous thrombosis, describing the mechanisms by which EVs affect thrombosis and their potential clinical applications. Full article
(This article belongs to the Special Issue Molecular and Cellular Basis of Thrombotic Diseases)
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Open AccessReview
Thrombosis Risk Associated with Head and Neck Cancer: A Review
Int. J. Mol. Sci. 2019, 20(11), 2838; https://doi.org/10.3390/ijms20112838 - 11 Jun 2019
Cited by 1
Abstract
Venous thromboembolism (VTE) is a common complication for cancer patients. VTE-associated risk varies according to the type of tumor disease. Head and neck cancer is a common cancer worldwide, and most tumors are squamous cell carcinomas due to tobacco and alcohol abuse. The [...] Read more.
Venous thromboembolism (VTE) is a common complication for cancer patients. VTE-associated risk varies according to the type of tumor disease. Head and neck cancer is a common cancer worldwide, and most tumors are squamous cell carcinomas due to tobacco and alcohol abuse. The risk of VTE associated with head and neck (H&N) cancer is considered empirically low, but despite the high incidence of H&N cancer, few data are available on this cancer; thus, it is difficult to state the risk of VTE. Our review aims to clarify this situation and tries to assess the real VTE risk associated with H&N cancer. We report that most clinical studies have concluded that there is a very low thrombosis risk associated with H&N cancer. Even with the biases that often exist, this clinical review seems to confirm that the risk of VTE was empirically hypothesized. Furthermore, we highlight that H&N cancer has all the biological features of a cancer associated with a high thrombosis risk, including a strong expression of procoagulant proteins, modified thrombosis/fibrinolysis mechanisms, and secretions of procoagulant microparticles and procoagulant cytokines. Thus, this is a paradoxical situation, and some undiscovered mechanisms that could explain this clinical biological ambivalence might exist. Full article
(This article belongs to the Special Issue Molecular and Cellular Basis of Thrombotic Diseases)
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