scholarly journals ROS in Platelet Biology: Functional Aspects and Methodological Insights

2020 ◽  
Vol 21 (14) ◽  
pp. 4866 ◽  
Author(s):  
Elena Masselli ◽  
Giulia Pozzi ◽  
Mauro Vaccarezza ◽  
Prisco Mirandola ◽  
Daniela Galli ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Molecular Mechanisms ◽  
Redox Balance ◽  
Ros Production ◽  
Thrombotic Risk ◽  
Disease Biomarkers ◽  
Redox Biology ◽  
Napdh Oxidase ◽  
Functional Aspects ◽  
Platelet Functions

Reactive oxygen species (ROS) and mitochondria play a pivotal role in regulating platelet functions. Platelet activation determines a drastic change in redox balance and in platelet metabolism. Indeed, several signaling pathways have been demonstrated to induce ROS production by NAPDH oxidase (NOX) and mitochondria, upon platelet activation. Platelet-derived ROS, in turn, boost further ROS production and consequent platelet activation, adhesion and recruitment in an auto-amplifying loop. This vicious circle results in a platelet procoagulant phenotype and apoptosis, both accounting for the high thrombotic risk in oxidative stress-related diseases. This review sought to elucidate molecular mechanisms underlying ROS production upon platelet activation and the effects of an altered redox balance on platelet function, focusing on the main advances that have been made in platelet redox biology. Furthermore, given the increasing interest in this field, we also describe the up-to-date methods for detecting platelets, ROS and the platelet bioenergetic profile, which have been proposed as potential disease biomarkers.

scholarly journals Reactive Oxygen Species: Not Omnipresent but Important in Many Locations

2021 ◽  
Vol 9 ◽  
Author(s):  
Marc Herb ◽  
Alexander Gluschko ◽  
Michael Schramm
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Redox Balance ◽  
Ros Production ◽  
Oxygen Species ◽  
Cellular Compartment ◽  
Whole Cell ◽  
Redox Biology ◽  
Cellular Source ◽  
The One

Reactive oxygen species (ROS), such as the superoxide anion or hydrogen peroxide, have been established over decades of research as, on the one hand, important and versatile molecules involved in a plethora of homeostatic processes and, on the other hand, as inducers of damage, pathologies and diseases. Which effects ROS induce, strongly depends on the cell type and the source, amount, duration and location of ROS production. Similar to cellular pH and calcium levels, which are both strictly regulated and only altered by the cell when necessary, the redox balance of the cell is also tightly regulated, not only on the level of the whole cell but in every cellular compartment. However, a still widespread view present in the scientific community is that the location of ROS production is of no major importance and that ROS randomly diffuse from their cellular source of production throughout the whole cell and hit their redox-sensitive targets when passing by. Yet, evidence is growing that cells regulate ROS production and therefore their redox balance by strictly controlling ROS source activation as well as localization, amount and duration of ROS production. Hopefully, future studies in the field of redox biology will consider these factors and analyze cellular ROS more specifically in order to revise the view of ROS as freely flowing through the cell.

scholarly journals The class I phosphoinositide 3-kinases α and β control antiphospholipid antibodies-induced platelet activation

2016 ◽  
Vol 115 (06) ◽  
pp. 1138-1146 ◽  
Author(s):  
Pierre-Alexandre Laurent ◽  
Cédric Garcia ◽  
Marie-Pierre Gratacap ◽  
Bart Vanhaesebroeck ◽  
Pierre Sié ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Antiphospholipid Antibodies ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Collagen Matrix ◽  
Thrombotic Risk ◽  
Pregnancy Morbidity ◽  
Phosphoinositide 3 Kinase

SummaryAntiphospholipid syndrome (APS) is an autoimmune disease characterised by the presence of antiphospholipid antibodies (aPL) associated with increased thrombotic risk and pregnancy morbidity. Although aPL are heterogeneous auto-antibodies, the major pathogenic target is the plasma protein β2-glycoprotein 1. The molecular mechanisms of platelet activation by aPL remain poorly understood. Here, we explored the role of the class IA phosphoinositide 3-kinase (PI3K) α and β isoforms in platelet activation by aPL. Compared to control IgG from healthy individuals, the IgG fraction isolated from patients with APS potentiates platelet aggregation induced by low dose of thrombin in vitro and increases platelet adhesion and thrombus growth on a collagen matrix under arterial shear rate through a mechanism involving glycoprotein Ib (GPIb) and Toll Like Receptor 2 (TLR-2). Using isoforms-selective pharmacological PI3K inhibitors and mice with megakaryocyte/platelet lineage-specific inactivation of class IA PI3K isoforms, we demonstrate a critical role of the PI3Kβ and PI3Kα isoforms in platelet activation induced by aPL. Our data show that aPL potentiate platelet activation through GPIbα and TLR-2 via a mechanism involving the class IA PI3Kα and β isoforms, which represent new potential therapeutic targets in the prevention or treatment of thrombotic events in patients with APS.

Increased Thromboxane Biosynthesis in Essential Thrombocythemia

1995 ◽  
Vol 74 (05) ◽  
pp. 1225-1230 ◽  
Author(s):  
Bianca Rocca ◽  
Giovanni Ciabattoni ◽  
Raffaele Tartaglione ◽  
Sergio Cortelazzo ◽  
Tiziano Barbui ◽  
...  
Keyword(s):  
Platelet Count ◽  
Platelet Activation ◽  
Essential Thrombocythemia ◽  
Therapeutic Strategy ◽  
Low Dose ◽  
Thrombotic Risk ◽  
Dose Aspirin ◽  
Gender And Age ◽  
Low Dose Aspirin

SummaryIn order to investigate the in vivo thromboxane (TX) biosynthesis in essential thromboeythemia (ET), we measured the urinary exeretion of the major enzymatic metabolites of TXB2, 11-dehydro-TXB2 and 2,3-dinor-TXB2 in 40 ET patients as well as in 26 gender- and age-matched controls. Urinary 11-dehydro-TXB2 was significantly higher (p <0.001) in thrombocythemic patients (4,063 ± 3,408 pg/mg creatinine; mean ± SD) than in controls (504 ± 267 pg/mg creatinine), with 34 patients (85%) having 11-dehydro-TXB2 >2 SD above the control mean. Patients with platelet number <1,000 × 109/1 (n = 25) had significantly higher (p <0.05) 11 -dehydro-TXB2 excretion than patients with higher platelet count (4,765 ± 3,870 pg/mg creatinine, n = 25, versus 2,279 ± 1,874 pg/mg creatinine, n = 15). Average excretion values of patients aging >55 was significantly higher than in the younger group (4,784 ± 3,948 pg/mg creatinine, n = 24, versus 2,405 ± 1,885 pg/mg creatinine, n = 16, p <0.05). Low-dose aspirin (50 mg/d for 7 days) largely suppressed 11-dehydro-TXB2 excretion in 7 thrombocythemic patients, thus suggesting that platelets were the main source of enhanced TXA2 biosynthesis. The platelet count-corrected 11-dehydro-TXB2 excretion was positively correlated with age (r = 0.325, n = 40, p <0.05) and inversely correlated with platelet count (r = -0.381, n = 40, p <0.05). In addition 11 out of 13 (85%) patients having increased count-corrected 11-dehydro-TXB2 excretion, belonged to the subgroup with age >55 and platelet count <1,000 × 1099/1. We conclude that in essential thrombocythemia: 1) enhanced 11-dehydro-TXB2 excretion largely reflects platelet activation in vivo;2) age as well as platelet count appear to influence the determinants of platelet activation in this setting, and can help in assessing the thrombotic risk and therapeutic strategy in individual patients.

scholarly journals Platelet-derived lysophosphatidic acid mediated LPAR1 activation as a therapeutic target for osteosarcoma metastasis

Oncogene ◽  
2021 ◽  
Author(s):  
Satoshi Takagi ◽  
Yuki Sasaki ◽  
Sumie Koike ◽  
Ai Takemoto ◽  
Yosuke Seto ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Pulmonary Metastasis ◽  
Lysophosphatidic Acid ◽  
Therapeutic Intervention ◽  
Molecular Mechanisms ◽  
Morphological Changes ◽  
Osteosarcoma Cells ◽  
Invasion And Metastasis ◽  
Platelet Releasate

AbstractOsteosarcoma is the most common primary malignant bone cancer, with high rates of pulmonary metastasis. Osteosarcoma patients with pulmonary metastasis have worse prognosis than those with localized disease, leading to dramatically reduced survival rates. Therefore, understanding the biological characteristics of metastatic osteosarcoma and the molecular mechanisms of invasion and metastasis of osteosarcoma cells will lead to the development of innovative therapeutic intervention for advanced osteosarcoma. Here, we identified that osteosarcoma cells commonly exhibit high platelet activation-inducing characteristics, and molecules released from activated platelets promote the invasiveness of osteosarcoma cells. Given that heat-denatured platelet releasate maintained the ability to promote osteosarcoma invasion, we focused on heat-tolerant molecules, such as lipid mediators in the platelet releasate. Osteosarcoma-induced platelet activation leads to abundant lysophosphatidic acid (LPA) release. Exposure to LPA or platelet releasate induced morphological changes and increased invasiveness of osteosarcoma cells. By analyzing publicly available transcriptome datasets and our in-house osteosarcoma patient-derived xenograft tumors, we found that LPA receptor 1 (LPAR1) is notably upregulated in osteosarcoma. LPAR1 gene KO in osteosarcoma cells abolished the platelet-mediated osteosarcoma invasion in vitro and the formation of early pulmonary metastatic foci in experimental pulmonary metastasis models. Of note, the pharmacological inhibition of LPAR1 by the orally available LPAR1 antagonist, ONO-7300243, prevented pulmonary metastasis of osteosarcoma in the mouse models. These results indicate that the LPA–LPAR1 axis is essential for the osteosarcoma invasion and metastasis, and targeting LPAR1 would be a promising therapeutic intervention for advanced osteosarcoma.

scholarly journals Physical Activity and Redox Balance in the Elderly: Signal Transduction Mechanisms

2021 ◽  
Vol 11 (5) ◽  
pp. 2228
Author(s):  
Daniela Galli ◽  
Cecilia Carubbi ◽  
Elena Masselli ◽  
Mauro Vaccarezza ◽  
Valentina Presta ◽  
...  
Keyword(s):  
Physical Activity ◽  
Molecular Mechanisms ◽  
Vascular Tissue ◽  
The Elderly ◽  
Redox Balance ◽  
Antioxidant Systems ◽  
Targeted Prevention ◽  
Individual Subject ◽  
Aged People ◽  
The Individual

Reactive Oxygen Species (ROS) are molecules naturally produced by cells. If their levels are too high, the cellular antioxidant machinery intervenes to bring back their quantity to physiological conditions. Since aging often induces malfunctioning in this machinery, ROS are considered an effective cause of age-associated diseases. Exercise stimulates ROS production on one side, and the antioxidant systems on the other side. The effects of exercise on oxidative stress markers have been shown in blood, vascular tissue, brain, cardiac and skeletal muscle, both in young and aged people. However, the intensity and volume of exercise and the individual subject characteristics are important to envisage future strategies to adequately personalize the balance of the oxidant/antioxidant environment. Here, we reviewed the literature that deals with the effects of physical activity on redox balance in young and aged people, with insights into the molecular mechanisms involved. Although many molecular pathways are involved, we are still far from a comprehensive view of the mechanisms that stand behind the effects of physical activity during aging. Although we believe that future precision medicine will be able to transform exercise administration from wellness to targeted prevention, as yet we admit that the topic is still in its infancy.

Quinidine-induced potentiation of cardiovascular effects of nitrendipine: functional aspects and possible molecular mechanisms

1995 ◽  
Vol 351 (6) ◽  
Author(s):  
Stefan Herzig ◽  
Julia Jischa ◽  
Antje Beinhauer ◽  
Bettina Geirhos ◽  
Kristin Tacke ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Cardiovascular Effects ◽  
Functional Aspects

scholarly journals Vascular Protective Role of Samul-Tang in HUVECs: Involvement of Nrf2/HO-1 and NO

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Eun Sik Choi ◽  
Yun Jung Lee ◽  
Chang Seob Seo ◽  
Jung Joo Yoon ◽  
Byung Hyuk Han ◽  
...  
Keyword(s):  
Vascular Endothelium ◽  
Molecular Mechanisms ◽  
Water Extract ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Ros Production ◽  
Herbal Formula ◽  
Protective Effects ◽  
Monocyte Adhesion

Samul-Tang (Si-Wu-Tang, SMT), composed of four medicinal herbs, is a well-known herbal formula treating hematological disorder or gynecologic disease. However, vascular protective effects of SMT and its molecular mechanisms on the vascular endothelium, known as the central spot of vascular inflammatory process, are not reported. The aim of this study was to investigate vascular protective effects of SMT water extract in human umbilical vein endothelial cells (HUVECs). Water extract of SMT was prepared and identified by HPLC-PDA analysis. Expression of cell adhesion molecules (CAMs) and heme oxygenase-1 (HO-1) and translocation of nuclear factor-kappa B (NF-κB) and nuclear factor-erythroid 2-related factor 2 (Nrf2) were determined by western blot. Nuclear localization of NF-κB and Nrf2 was visualized by immunofluorescence and DNA binding activity of NF-κB was measured. ROS production, HL-60 monocyte adhesion, and intracellular nitric oxide (NO) were also measured using a fluorescent indicator. SMT suppressed NF-κB translocation and activation as well as expression of CAMs, monocyte adhesion, and ROS production induced by TNF-αin HUVECs. SMT treated HUVECs showed upregulation of HO-1 and NO which are responsible for vascular protective action. Our study suggests that SMT, a traditionally used herbal formula, protects the vascular endothelium from inflammation and might be used as a promising vascular protective drug.

scholarly journals Induction of soluble platelet activation markers and FXIII deficiency promote COVID-19 severity

2021 ◽  
Author(s):  
Abaher O. Al-Tamimi ◽  
Ayesha M. Yusuf ◽  
Manju N. Jayakumar ◽  
Abdul W. Ansari ◽  
Mona Elhassan ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Platelet Activation ◽  
Molecular Mechanisms ◽  
Plasminogen Activator Inhibitor ◽  
Cd40 Ligand ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activation Markers ◽  
Pathway Activation ◽  
Coagulation Dysfunction ◽  
Fxiii Deficiency

Coagulation dysfunction and thromboembolism emerge as strong comorbidity factors in severe COVID-19 patients. However, the underlying pathomechanisms are largely undefined. Here, we sought to identify the potential molecular mechanisms of SARS-CoV-2 mediated coagulopathy and thromboembolism. A broader investigation was conducted including hospitalized COVID-19 patients with (severe cases that required intensive care) or without pneumonia (moderate cases). Phenotypic and molecular characterizations were performed employing basic coagulation tests, flow cytometry-based multiplex assays, and ELISA. The investigations revealed induction of plasma P-selectin and CD40 ligand (sCD40L) in moderate COVID-19 cases which were significantly abolished with the progression of COVID-19 severity. Moreover, a profound reduction in plasma tissue factor pathway inhibitor (TFPI) and FXIII were identified particularly in the severe COVID-19. Further analysis revealed a profound induction of fibrinogen in both moderate and severe patients. Interestingly, an elevated plasminogen activator inhibitor-1 more prominently in moderate, and tissue plasminogen activator (tPA) particularly in severe COVID-19 cases were observed. Particularly, the levels of fibrinogen and tPA directly correlated with the severity of COVID-19. In summary, SARS-CoV-2 infection induces the levels of platelet activation markers soluble P-selectin and sCD40L in hospitalized COVID-19 patients. Furthermore, an attenuated level of TFPI indicates TF pathway activation and, acquired FXIII deficiency likely plays a key role in thrombus instability and promotes thromboembolism in severe cases. The progression of COVID-19 severity could be limited with anti-platelet in combination with recombinantTFPI treatment. Furthermore, thromboembolic events in severe COVID-19 patients could be minimized if treated with recombinantFXIII in combination with LMW heparin.

scholarly journals Antioxidant and Anti-inflammatory Mechanisms of Astaxanthin in Cardiovascular Diseases

2020 ◽  
Author(s):  
Carolina Parga Martins Pereira ◽  
Ana Carolina Remondi Souza ◽  
Andrea Rodrigues Vasconcelos ◽  
Pietra Sacramento Prado ◽  
José João Name
Keyword(s):  
Cardiovascular Diseases ◽  
Molecular Mechanisms ◽  
Cardiovascular Health ◽  
Redox Balance ◽  
Cellular Mechanisms ◽  
Positive Effects ◽  
Antioxidant Agents ◽  
Therapeutic Properties ◽  
Anti Inflammatory ◽  
Preclinical And Clinical Studies

Cardiovascular disease is the most common cause of death. Oxidative stress and inflammation are pathophysiological processes involved in the development of cardiovascular diseases, so anti-inflammatory and antioxidant agents that modulate redox balance have become the targets of research to evaluate their molecular mechanisms and therapeutic properties. Astaxanthin, a carotenoid of the xanthophyll group, has potent antioxidant effects due to its molecular structure and its arrangement in the plasma membrane, factors that favor the neutralization of reactive oxygen and nitrogen species. This carotenoid also stands out for its anti-inflammatory activity, possibly interrelated with its antioxidant effect, as well as for its modulation of lipid and glucose metabolism. Considering the potential positive effects of astaxanthin on cardiovascular health evidenced by preclinical and clinical studies, this paper describes the molecular and cellular mechanisms related to the antioxidant and anti-inflammatory properties of this carotenoid in cardiovascular diseases, especially atherosclerosis.

scholarly journals Secreted Frizzled Related Proteins in Cardiovascular and Metabolic Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Hua Guan ◽  
Jin Zhang ◽  
Jing Luan ◽  
Hao Xu ◽  
Zhenghao Huang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Structural Characteristics ◽  
Wnt Signaling Pathway ◽  
Secreted Protein ◽  
Related Protein ◽  
Disease Biomarkers ◽  
Protein Levels ◽  
Related Proteins

Abnormal gene expression and secreted protein levels are accompanied by extensive pathological changes. Secreted frizzled related protein (SFRP) family members are antagonistic inhibitors of the Wnt signaling pathway, and they were recently found to be involved in the pathogenesis of a variety of metabolic diseases, which has led to extensive interest in SFRPs. Previous reports highlighted the importance of SFRPs in lipid metabolism, obesity, type 2 diabetes mellitus and cardiovascular diseases. In this review, we provide a detailed introduction of SFRPs, including their structural characteristics, receptors, inhibitors, signaling pathways and metabolic disease impacts. In addition to summarizing the pathologies and potential molecular mechanisms associated with SFRPs, this review further suggests the potential future use of SFRPs as disease biomarkers therapeutic targets.

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