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Molecular Research on Platelet Activity in Health and Disease 2023

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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: 20 September 2024 | Viewed by 10274

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Special Issue Editors

Dr. Valeria Gasperi

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Guest Editor

Department of Experimental Medicine, Tor Vergata University of Rome, Via Montpellier 1, 00133 Rome, Italy
Interests: cancer biology; microRNAs; epigenetics; apoptosis and differentiation; platelets; inflammation; cell-to-cell crosstalk; bioactive lipids
Special Issues, Collections and Topics in MDPI journals

Dr. Isabella Savini

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Guest Editor

Department of Experimental Medicine, Tor Vergata University of Rome, Via Montpellier 1, 00133 Rome, Italy
Interests: nutrition; platelets; redox state; phenolic compounds; cardiovascular diseases; obesity; metabolic syndrome
Special Issues, Collections and Topics in MDPI journals

Dr. Maria Valeria Catani

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Guest Editor

Department of Experimental Medicine, Tor Vergata University of Rome, Via Montpellier 1, 00133 Rome, Italy
Interests: platelets; oxidative stress; cancer; vitamin C; blood coagulation; inflammation; apoptosis; bioactive lipids; redox-sensitive transcription factors; microRNAs
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Platelets are small anucleated cytoplasmic fragments derived from large megakaryocytes residing in bone marrow that are primarily recognized for their fundamental role in haemostasis and thrombosis. In response to vascular injury, platelets quickly adhere to sub-endothelial matrix proteins, through specific adhesion-signalling receptors whose activation leads to a cascade of events resulting in platelet spreading, granule secretion, aggregation and clot retraction.

To date, a large body of evidence has highlighted the ability of platelets to act as multifunctional cells, which actively influence a widespread range of apparently unrelated patho–physiological events. Platelets, indeed, play a central role in inflammation, an underlying cause in several pathologies (among them cardiovascular disease, obesity, metabolic syndrome and gastrointestinal diseases) as well as in infection, cancer, neurodegeneration and other brain dysfunctions.

For readers, this Special Issue, “Molecular Research on Platelet Activity in Health and Disease”, will provide an up-to-date description of the more intriguing aspects of platelet biology, highly relevant to human diseases.

Dr. Valeria Gasperi
Dr. Isabella Savini
Dr. Maria Valeria Catani
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
hemostasis
cancer
microRNA
inflammatory diseases
cell-to-cell crosstalk
endothelium
infection
brain disease

Related Special Issue

Molecular Research on Platelet Activity in Health and Disease 3.0 in International Journal of Molecular Sciences (12 articles)

Published Papers (5 papers)

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Research

15 pages, 2261 KiB

Open AccessArticle

Daidzein Inhibits Human Platelet Activation by Downregulating Thromboxane A₂ Production and Granule Release, Regardless of COX-1 Activity

by Hyun-Jin Hong, Gi-Suk Nam and Kyung-Soo Nam

Int. J. Mol. Sci. 2023, 24(15), 11985; https://doi.org/10.3390/ijms241511985 - 26 Jul 2023

Cited by 1 | Viewed by 1140

Abstract

Platelets play crucial roles in cardiovascular diseases (CVDs) by regulating hemostasis and blood coagulation at sites of blood vessel damage. Accumulating evidence indicates daidzein inhibits platelet activation, but the mechanism involved has not been elucidated. Thus, in this study, we investigated the mechanism responsible for the inhibition of collagen-induced platelet aggregation by daidzein. We found that in collagen-induced platelets, daidzein suppressed the production of thromboxane A₂ (TXA₂), a molecule involved in platelet activation and aggregation, by inhibiting the cytosolic phospholipase A₂ (cPLA₂) signaling pathway. However, daidzein did not affect cyclooxygenase-1 (COX-1). Furthermore, daidzein attenuated the PI3K/PDK1/Akt/GSK3αβ and MAPK (p38, ERK) signaling pathways, increased the phosphorylation of inositol trisphosphate receptor1 (IP₃R1) and vasodilator-stimulated phosphoprotein (VASP), and increased the level of cyclic adenosine monophosphate (cAMP). These results suggest that daidzein inhibits granule release (ATP, serotonin, P-selectin), integrin α_IIbβ₃ activation, and clot retraction. Taken together, our study demonstrates that daidzein inhibits collagen-induced platelet aggregation and suggests that daidzein has therapeutic potential for the treatment of platelet aggregation-related diseases such as atherosclerosis and thrombosis. Full article

(This article belongs to the Special Issue Molecular Research on Platelet Activity in Health and Disease 2023)

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14 pages, 1122 KiB

Open AccessArticle

Biomarkers of Exposure and Potential Harm in Two Weeks of Smoking Abstinence: Changes in Biomarkers of Platelet Function, Oxidative Stress, and Inflammation

by Patrudu Makena, Eric Scott, Peter Chen, Hsiao-Pin Liu, Bobbette A. Jones and Gaddamanugu L. Prasad

Int. J. Mol. Sci. 2023, 24(7), 6286; https://doi.org/10.3390/ijms24076286 - 27 Mar 2023

Cited by 2 | Viewed by 1698

Abstract

: Chronic cigarette smoking is a major risk factor for many serious diseases. While complete cessation of smoking is the best option to reduce harm from smoking, adverse impacts of smoking on health could persist for several years after cessation. Therefore, Biomarkers of Potential Harm (BoPH) are useful in interim evaluations of the beneficial effects of smoking cessation or switching to potentially lower-risk tobacco products. A 14-day smoking abstinence study was conducted under clinical confinement conditions and enrolled 70 subjects into younger (24–34 years, n = 33) and older (35–60 years, n = 37) age cohorts. Biomarkers of Exposure (BoE), which indicate exposure to nicotine and other toxicants, were measured at baseline, 7 and 14 days. Several BoPH including previously identified eicosanoids (leukotriene 4 (LTE4) and 2,3-dinor thromboxane ₂ (2,3-d-TXB₂) and others were evaluated. Significant declines in BoE, LTE_4, 2,3-d-TXB₂, neutrophils, WBC and select RBC, and arterial blood gas parameters were observed in both age cohorts at Days 7 and 14 compared to baseline, while other BoPH (e.g., FeNO) showed age-related effects. Rapid and reproducible reductions in LTE₄, 2,3-d-TXB₂ WBC, and neutrophil counts were consistently detected following smoking abstinence, indicating the value of these markers as useful BoPH. Full article

(This article belongs to the Special Issue Molecular Research on Platelet Activity in Health and Disease 2023)

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22 pages, 4381 KiB

Open AccessArticle

A New Role of NAP1L1 in Megakaryocytes and Human Platelets

by Martin Freitag and Hansjörg Schwertz

Int. J. Mol. Sci. 2022, 23(23), 14694; https://doi.org/10.3390/ijms232314694 - 24 Nov 2022

Cited by 1 | Viewed by 1962

Abstract

Platelets (PLTs) are anucleate and considered incapable of nuclear functions. Contrastingly, nuclear proteins were detected in human PLTs. For most of these proteins, it is unclear if nuclear or alternatively assigned functions are performed, a question we wanted to address for nuclear assembly protein 1like 1 (NAP1L1). Using a wide array of molecular methods, including RNAseq, co-IP, overexpression and functional assays, we explored expression pattern and functionality of NAP1L1 in PLTs, and CD34⁺-derived megakaryocytes (MKs). NAP1L1 is expressed in PLTs and MKs. Co-IP experiments revealed that dihydrolipolylysine-residue acetyltransferase (DLAT encoded protein PDC-E2, ODP2) dynamically interacts with NAP1L1. PDC-E2 is part of the mitochondrial pyruvate-dehydrogenase (PDH) multi-enzyme complex, playing a crucial role in maintaining cellular respiration, and promoting ATP-synthesis via the respiratory chain. Since altered mitochondrial function is a hallmark of infectious syndromes, we analyzed PDH activity in PLTs from septic patients demonstrating increased activity, paralleling NAP1L1 expression levels. MKs PDH activity decreased following an LPS-challenge. Furthermore, overexpression of NAP1L1 significantly altered the ability of MKs to form proplatelet extensions, diminishing thrombopoiesis. These results indicate that NAP1L1 performs in other than nucleosome-assembly functions in PTLs and MKs, binding a key mitochondrial protein as a potential chaperone, and gatekeeper, influencing PDH activity and thrombopoiesis. Full article

(This article belongs to the Special Issue Molecular Research on Platelet Activity in Health and Disease 2023)

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15 pages, 2597 KiB

Open AccessArticle

A Novel Antibody Targeting the Second Extracellular Loop of the Serotonin 5-HT2A Receptor Inhibits Platelet Function

by Jean E. M. Ramirez, Ahmed B. Alarabi, Fadi T. Khasawneh and Fatima Z. Alshbool

Int. J. Mol. Sci. 2022, 23(15), 8794; https://doi.org/10.3390/ijms23158794 - 08 Aug 2022

Cited by 3 | Viewed by 2074

Abstract

Serotonin (5-hydroxytriptamine or 5-HT) is known to be a weak platelet agonist, and is involved in thrombus formation. While 5-HT cannot induce platelet aggregation on its own, when secreted from the alpha granules, it binds to its G-protein Coupled Receptor (GPCR; i.e., 5HT_2AR), thereby acting to amplify platelet functional responses (e.g., aggregation). Thus, 5HT_2AR-mediated responses are more involved in the secondary amplification of platelet aggregation in the growing thrombus. Therefore, even though 5-HT can be seen as a weak inducer of platelet activation, it is an important amplifier of aggregation triggered by agonists such as ADP, collagen, and epinephrine, thereby enhancing thrombogenesis. The 5HT_2AR/5HT_2A signaling pathway is of clinical interest to the scientific and medical communities as it has been implicated in the genesis of several forms of cardiovascular disorders. However, efforts to develop antagonists for 5HT_2AR as therapeutic agents in cardiovascular diseases have thus far failed due to these reagents having deleterious side-effects, and/or to lack of selectivity, amongst other reasons. In light of research efforts that identified that the 5HT_2AR ligand binding domain resides in the second extracellular loop (EL2; amino acids P²⁰⁹-N²³³), we developed an antibody, i.e., referred to as 5HT_2ARAb, against the EL2 region, and characterized its pharmacological activity in the context of platelets. Thus, we utilized platelets from healthy human donors, as well as C57BL/6J mice (10–12 weeks old) to analyze the inhibitory effects of the 5HT_2ARAb on platelet activation in vitro, ex vivo, and on thrombogenesis in vivo as well as on 5HT_2AR ligand binding. Our results indicate that the 5HT_2ARAb inhibits 5-HT-enhanced platelet activation in vitro and ex vivo, but has no apparent effects on that which is agonist-induced. The 5HT_2ARAb was also found to prolong the thrombus occlusion time, and it did so without modulating the tail bleeding time, in mice unlike the P2Y12 antagonist clopidogrel and the 5HT_2AR antagonist ketanserin. Moreover, it was found that the 5HT_2ARAb does so by directly antagonizing the platelet 5HT_2AR. Our findings document that the custom-made 5HT_2ARAb exhibits platelet function blocking activity and protects against thrombogenesis without impairing normal hemostasis. Full article

(This article belongs to the Special Issue Molecular Research on Platelet Activity in Health and Disease 2023)

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17 pages, 6527 KiB

Open AccessArticle

Platelet-Derived miR-126-3p Directly Targets AKT2 and Exerts Anti-Tumor Effects in Breast Cancer Cells: Further Insights in Platelet-Cancer Interplay

by Matteo Sibilano, Valentina Tullio, Gaspare Adorno, Isabella Savini, Valeria Gasperi and Maria Valeria Catani

Int. J. Mol. Sci. 2022, 23(10), 5484; https://doi.org/10.3390/ijms23105484 - 13 May 2022

Cited by 15 | Viewed by 2296

Abstract

Among the surrounding cells influencing tumor biology, platelets are recognized as novel players as they release microvesicles (MVs) that, once delivered to cancer cells, modulate signaling pathways related to cell growth and dissemination. We have previously shown that physiological delivery of platelet MVs enriched in miR-126 exerted anti-tumor effects in different breast cancer (BC) cell lines. Here, we seek further insight by identifying AKT2 kinase as a novel miR-126-3p direct target, as assessed by bioinformatic analysis and validated by luciferase assay. Both ectopic expression and platelet MV-mediated delivery of miR-126-3p downregulated AKT2 expression, thus suppressing proliferating and invading properties, in either triple negative (BT549 cells) or less aggressive Luminal A (MCF-7 cells) BC subtypes. Accordingly, as shown by bioinformatic analysis, both high miR-126 and low AKT2 levels were associated with favorable long-term prognosis in BC patients. Our results, together with the literature data, indicate that miR-126-3p exerts suppressor activity by specifically targeting components of the PIK3/AKT signaling cascade. Therefore, management of platelet-derived MV production and selective delivery of miR-126-3p to tumor cells may represent a useful tool in multimodal therapeutic approaches in BC patients. Full article

(This article belongs to the Special Issue Molecular Research on Platelet Activity in Health and Disease 2023)

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