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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 (30 December 2023) | Viewed by 15627

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Dr. Isabella Russo

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Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole, 10, Orbassano, I-10043 Turin, Italy
Interests: platelets function; nitric oxide; haemostasis; thrombosis; anti-platelet drugs; platelet dysfunction in metabolic diseases
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Special Issue Information

Dear Colleagues,

Platelets, best known as the primary mediators of hemostasis and thrombosis, are a critical component of blood vessel walls. As secretory cells, platelets can release multiple substances from storage granules, biomediators, and membrane vesicles, influencing both physiological and pathophysiological processes. Conversely, platelets can uptake plasma and cellular components, influencing platelet responsiveness. The analysis of platelet function through the development of powerful imaging techniques, as well as the identification of cells and new molecules that regulate their activation and aggregation within vessels, are instrumental in order to better understand the mechanisms through which platelets protect or damage organisms. These analyses provide useful information for studying the pathogenesis of many disease states.

This Special Issue of the International Journal of Molecular Sciences, titled “New Advances in Platelet Biology and Functions”, will focus on recent advances in platelet function research, such as platelet action or the release of substances or micro-particles containing platelet miRNA, enzymes, proteins, and small molecules with roles in healthy conditions and as drivers of immunity, inflammation, angiogenesis, and tumor growth. Contributions on these and related topics are welcome, including original research and reviews. We particularly welcome submissions from postdocs, PhD students, and young researchers.

Dr. Isabella Russo
Guest Editor

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Keywords

platelet microparticles
thrombosis
inflammation
oxidative stress
antiplatelet drug
signal transduction
immunity
tumor growth

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Published Papers (8 papers)

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Research

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12 pages, 1925 KiB

Open AccessArticle

Inflammatory and Prothrombotic Biomarkers Contribute to the Persistence of Sequelae in Recovered COVID-19 Patients

by Nallely Garcia-Larragoiti, Alan Cano-Mendez, Yeny Jimenez-Vega, Mercedes Trujillo, Patricia Guzman-Cancino, Yesenia Ambriz-Murillo and Martha Eva Viveros-Sandoval

Int. J. Mol. Sci. 2023, 24(24), 17468; https://doi.org/10.3390/ijms242417468 - 14 Dec 2023

Cited by 4 | Viewed by 1353

Abstract

The presence of long COVID (LC) following SARS-CoV-2 infection is a common condition that affects the quality of life of patients and represents a diagnostic challenge due to the diversity of symptoms that may coexist. We still do not have accurate information regarding the pathophysiological pathways that generate the presence of LC, and so it is important to know the inflammatory and immunothrombotic biomarker profiles and their implications in order to characterize risk subgroups and establish early therapeutic strategies. We performed the determination of inflammatory and immunothrombotic biomarkers in volunteers with previous diagnoses of SARS-CoV-2. The inflammatory biomarkers were analyzed in plasma by flow cytometry, and we analyzed the von Willebrand factor (vWF) in the plasma samples using ELISA. The clinical variables and the presence or absence of long COVID symptoms were then analyzed. IL-6, sCD40L, p-Selectin, PSGL-1, PAI-1, tPA, D-Dimer, TF, and Factor IX levels were elevated in the groups with LC, especially in the subgroup of patients with metabolic syndrome (MetS). VWF levels were found to be increased in patients with sequelae and MetS. Our results confirmed the persistence of an active immunothrombotic state, and so it is important to identify the population at risk in order to provide adequate clinical follow-up. Full article

(This article belongs to the Special Issue New Advances in Platelet Biology and Functions)

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17 pages, 2472 KiB

Open AccessArticle

Genetic Variability in VEGFA Gene Influences the Effectiveness of Tennis Elbow Therapy with PRP: A Two-Year Prospective Cohort Study

by Paweł Niemiec, Alicja Jarosz, Anna Balcerzyk-Matić, Joanna Iwanicka, Tomasz Nowak, Tomasz Iwanicki, Marcin Gierek, Marcin Kalita, Wojciech Garczorz, Tomasz Francuz, Sylwia Górczyńska-Kosiorz, Wojciech Kania and Karol Szyluk

Int. J. Mol. Sci. 2023, 24(24), 17292; https://doi.org/10.3390/ijms242417292 - 9 Dec 2023

Cited by 1 | Viewed by 1207

Abstract

Vascular endothelial growth factor (VEGF) is implicated in both the etiology of tendinopathy and its healing process. Polymorphic variants of the VEGFA gene exhibit varied expression, which can influence the phenotype and treatment effectiveness. The aim of the present study was to analyze the influence of VEGFA gene variants on the effectiveness of tennis elbow therapy using platelet-rich plasma (PRP), measured through common patient-reported outcome measures (PROMs). A cohort of 107 patients (132 elbows) with tennis elbow was prospectively analyzed, with a two-year follow-up (at weeks 2, 4, 8, 12, 24, 52, and 104 after PRP injection). PROMs values were compared between variants of five VEGFA gene polymorphisms (rs699947 A>C, rs2010963 C>G, rs1413711 C>T, rs3024998 C>T and rs3025021 C>T) at each follow-up point. Patients with genotypes GG (rs2010963) and CC (rs3024998) had better response to PRP therapy (significantly fewer symptoms and limitations in the upper limb compared to carriers of alleles C and T, respectively). Polymorphisms influenced also selected hematological parameters. VEGFA gene polymorphisms (rs2010963 and rs3024998) appear to be significant treatment modifiers for tendinopathy, and their genotyping may serve as an effective tool for personalized patient selection for PRP therapy. Full article

(This article belongs to the Special Issue New Advances in Platelet Biology and Functions)

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18 pages, 1295 KiB

Open AccessArticle

Platelets as Potential Non-Traditional Cardiovascular Risk Factor—Analysis Performed in Healthy Donors

by Patrycja Szymańska, Bogusława Luzak, Przemysław Siarkiewicz and Jacek Golański

Int. J. Mol. Sci. 2023, 24(19), 14914; https://doi.org/10.3390/ijms241914914 - 5 Oct 2023

Cited by 5 | Viewed by 1585

Abstract

Abnormal lipid profile, increased glucose level, and elevated body weight are traditional cardiometabolic risk factors; however, the role of platelets in the development of cardiovascular disease (CVD) is increasingly being highlighted. The aim of this study was to select platelet-related parameters (non-genetic molecular and routine laboratory measurements) that may be associated with increased cardiovascular risk among healthy populations. We evaluated the level of platelet indices, platelet-based inflammatory markers, platelet reactivity parameters, and platelet reactive oxygen species (ROS) generation in relation to selected cardiometabolic risk factors. We noted the association between total cholesterol and LDL cholesterol with platelet aggregation and platelet ROS generation. We found the relationship between triglycerides, glucose, and body mass index with the relatively new multi-inflammatory indices (MII-1 and MII-3). Moreover, we noticed that the mean platelet volume-to-lymphocyte ratio in healthy subjects is not a good source of information about platelets and inflammation. We also highlighted that platelet-to-HDL-cholesterol ratio may be a promising prognostic cardiometabolic indicator. The association between platelet-related (especially molecular) and cardiometabolic parameters requires further research. However, the goal of this study was to shed light on the consideration of platelets as a non-traditional cardiovascular risk factor and a crucial element in identifying individuals at high-risk of developing CVD in the future. Full article

(This article belongs to the Special Issue New Advances in Platelet Biology and Functions)

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22 pages, 3395 KiB

Open AccessArticle

The Effect of Leukocyte- and Platelet-Rich Fibrin on Central and Peripheral Nervous System Neurons—Implications for Biomaterial Applicability

by Ivo Lambrichts, Esther Wolfs, Annelies Bronckaers, Pascal Gervois and Tim Vangansewinkel

Int. J. Mol. Sci. 2023, 24(18), 14314; https://doi.org/10.3390/ijms241814314 - 20 Sep 2023

Cited by 1 | Viewed by 1654

Abstract

Leukocyte- and Platelet-Rich Fibrin (L-PRF) is a second-generation platelet concentrate that is prepared directly from the patient’s own blood. It is widely used in the field of regenerative medicine, and to better understand its clinical applicability we aimed to further explore the biological properties and effects of L-PRF on cells from the central and peripheral nervous system. To this end, L-PRF was prepared from healthy human donors, and confocal, transmission, and scanning electron microscopy as well as secretome analysis were performed on these clots. In addition, functional assays were completed to determine the effect of L-PRF on neural stem cells (NSCs), primary cortical neurons (pCNs), and peripheral dorsal root ganglion (DRG) neurons. We observed that L-PRF consists of a dense but porous fibrin network, containing leukocytes and aggregates of activated platelets that are distributed throughout the clot. Antibody array and ELISA confirmed that it is a reservoir for a plethora of growth factors. Key molecules that are known to have an effect on neuronal cell functions such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) were slowly released over time from the clots. Next, we found that the L-PRF secretome had no significant effect on the proliferative and metabolic activity of NSCs, but it did act as a chemoattractant and improved the migration of these CNS-derived stem cells. More importantly, L-PRF growth factors had a detrimental effect on the survival of pCNs, and consequently, also interfered with their neurite outgrowth. In contrast, we found a positive effect on peripheral DRG neurons, and L-PRF growth factors improved their survival and significantly stimulated the outgrowth and branching of their neurites. Taken together, our study demonstrates the positive effects of the L-PRF secretome on peripheral neurons and supports its use in regenerative medicine but care should be taken when using it for CNS applications. Full article

(This article belongs to the Special Issue New Advances in Platelet Biology and Functions)

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10 pages, 575 KiB

Open AccessArticle

The Characterization and Evaluation of the Soluble Triggering Receptor Expressed on Myeloid Cells-like Transcript-1 in Stable Coronary Artery Disease

by Zaida Bayrón-Marrero, Siobhan Branfield, Javier Menéndez-Pérez, Benjamín Nieves-López, Laura Ospina, Yadira Cantres-Rosario, Loyda M. Melendez, Robert Hunter, Angelia Gibson, Gerónimo Maldonado-Martínez and A. Valance Washington

Int. J. Mol. Sci. 2023, 24(17), 13632; https://doi.org/10.3390/ijms241713632 - 4 Sep 2023

Cited by 1 | Viewed by 1413

Abstract

Platelets play crucial roles in the development and progression of coronary artery disease (CAD). The triggering receptor expressed in myeloid cells-like transcript-1 (TLT-1) is stored in platelet α granules, and activated platelets release a soluble fragment (sTLT-1). We set out to better characterize the constituent amino acids of sTLT-1 and to evaluate sTLT-1 for use as a biomarker in patients with stable CAD. We evaluated sTLT-1 release using immunoprecipitation and mass spectrometry and employed statistical methods to retrospectively correlate sTLT-1 concentrations, utilizing ELISA in plasma samples from 1510 patients with documented stable CAD. We identified TLT-1 residues to 133 in platelet releasates. ADAM17 cuts TLT-1, suggesting that S136 is the C-terminal amino acid in sTLT-1. Our results revealed that for CAD patients, sTLT-1 levels did not differ significantly according to primary outcomes of death or major cardiac event; however, patients with left ventricular (LV) dysfunction had significantly lower plasma sTLT-1 levels as compared to those with normal LV function (981.62 ± 1141 pg/mL vs. 1247.48 ± 1589 pg/mL; p = 0.003). When patients were stratified based on sTLT-1 peak frequency distribution (544 pg/mL), a significant association with congestive heart failure was identified (OR = 2.94; 1.040–8.282; p = 0.042), which could be explained by LV dysfunction. Full article

(This article belongs to the Special Issue New Advances in Platelet Biology and Functions)

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14 pages, 2457 KiB

Open AccessArticle

Cryopreserved Platelets in a Non-Toxic DMSO-Free Solution Maintain Hemostatic Function In Vitro

by Kristina Ehn, Agneta Wikman, Michael Uhlin and Per Sandgren

Int. J. Mol. Sci. 2023, 24(17), 13097; https://doi.org/10.3390/ijms241713097 - 23 Aug 2023

Cited by 2 | Viewed by 2277

Abstract

Dimethyl sulfoxide (DMSO) is regularly used as a cryoprotectant agent for the cryopreservation of platelets. However, DMSO is considered toxic. We therefore hypothesized that saline could be used as a non-toxic medium for the cryopreservation of platelets. Double-dose buffy coat platelets (n = 10) were divided and cryopreserved at −80 °C using 5–6% dimethyl sulfoxide (DMSO) or in NaCl (9 mg/mL). Paired testing was conducted pre-freeze, post-thaw (PT 1 h). Upon analysis, each bag was thawed and reconstituted in fresh plasma. Analyses included cell counts and the metabolic, phenotypic, and functional properties of the platelets together with thromboelastometry. The cryopreserved platelets showed several biochemical and ultrastructural changes compared to pre-freezing. Platelet recovery was approximately 17% higher in DMSO-free units (p < 0.001), but the platelet viability was reduced (p < 0.001). However, using controlled freezing (n = 6), the platelet viability was improved. The clot formation time (CFT) was comparable, but DMSO-free platelets showed slightly decreased maximum clot firmness (MCF) (p = 0.034). By reducing the reconstituted plasma volume, a reduced CFT and increased MCF were obtained (p < 0.001). This study demonstrates that platelets can be cryopreserved in saline without the addition of DMSO, with high recovery and maintained hemostatic function. However, controlled freezing is required to optimize platelet quality. Full article

(This article belongs to the Special Issue New Advances in Platelet Biology and Functions)

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Review

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20 pages, 1227 KiB

Open AccessReview

Crosstalk between Platelets and SARS-CoV-2: Implications in Thrombo-Inflammatory Complications in COVID-19

by Junyi Zhao, Xiafan Xu, Yifei Gao, Yijing Yu and Conglei Li

Int. J. Mol. Sci. 2023, 24(18), 14133; https://doi.org/10.3390/ijms241814133 - 15 Sep 2023

Cited by 5 | Viewed by 2071

Abstract

The SARS-CoV-2 virus, causing the devastating COVID-19 pandemic, has been reported to affect platelets and cause increased thrombotic events, hinting at the possible bidirectional interactions between platelets and the virus. In this review, we discuss the potential mechanisms underlying the increased thrombotic events as well as altered platelet count and activity in COVID-19. Inspired by existing knowledge on platelet–pathogen interactions, we propose several potential antiviral strategies that platelets might undertake to combat SARS-CoV-2, including their abilities to internalize the virus, release bioactive molecules to interfere with viral infection, and modulate the functions of immune cells. Moreover, we discuss current and potential platelet-targeted therapeutic strategies in controlling COVID-19, including antiplatelet drugs, anticoagulants, and inflammation-targeting treatments. These strategies have shown promise in clinical settings to alleviate the severity of thrombo-inflammatory complications and reduce the mortality rate among COVID-19 patients. In conclusion, an in-depth understanding of platelet–SARS-CoV-2 interactions may uncover novel mechanisms underlying severe COVID-19 complications and could provide new therapeutic avenues for managing this disease. Full article

(This article belongs to the Special Issue New Advances in Platelet Biology and Functions)

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27 pages, 2242 KiB

Open AccessReview

Advances in Platelet Rich Plasma-Derived Extracellular Vesicles for Regenerative Medicine: A Systematic-Narrative Review

by Eduardo Anitua, María Troya, Juan Manuel Falcon-Pérez, Silvia López-Sarrio, Esperanza González and Mohammad H. Alkhraisat

Int. J. Mol. Sci. 2023, 24(17), 13043; https://doi.org/10.3390/ijms241713043 - 22 Aug 2023

Cited by 19 | Viewed by 3263

Abstract

The use of platelet-rich plasma (PRP) has gained increasing interest in recent decades. The platelet secretome contains a multitude of growth factors, cytokines, chemokines, and other biological biomolecules. In recent years, developments in the field of platelets have led to new insights, and attention has been focused on the platelets’ released extracellular vesicles (EVs) and their role in intercellular communication. In this context, the aim of this review was to compile the current evidence on PRP-derived extracellular vesicles to identify the advantages and limitations fortheir use in the upcoming clinical applications. A total of 172 articles were identified during the systematic literature search through two databases (PubMed and Web of Science). Twenty publications met the inclusion criteria and were included in this review. According to the results, the use of PRP-EVs in the clinic is an emerging field of great interest that represents a promising therapeutic option, as their efficacy has been demonstrated in the majority of fields of applications included in this review. However, the lack of standardization along the procedures in both the field of PRP and the EVs makes it extremely challenging to compare results among studies. Establishing standardized conditions to ensure optimized and detailed protocols and define parameters such as the dose or the EV origin is therefore urgent. Further studies to elucidate the real contribution of EVs to PRP in terms of composition and functionality should also be performed. Nevertheless, research on the field provides promising results and a novel basis to deal with the regenerative medicine and drug delivery fields in the future. Full article

(This article belongs to the Special Issue New Advances in Platelet Biology and Functions)

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