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Journal of Biomechanical Engineering Apr 2022Shear-induced platelet activation is one of the critical outcomes when blood is exposed to elevated shear stress. Excessively activated platelets in the circulation can...
Shear-induced platelet activation is one of the critical outcomes when blood is exposed to elevated shear stress. Excessively activated platelets in the circulation can lead to thrombus formation and platelet consumption, resulting in serious adverse events such as thromboembolism and bleeding. While experimental observations reveal that it is related to the shear stress level and exposure time, the underlying mechanism of shear-induced platelet activation is not fully understood. Various models have been proposed to relate shear stress levels to platelet activation, yet most are modified from the empirically calibrated power-law model. Newly developed multiscale platelet models are tested as a promising approach to capture a single platelet's dynamic shape during activation, but it would be computationally expensive to employ it for a large-scale analysis. This paper summarizes the current numerical models used to study the shear-induced platelet activation and their computational applications in the risk assessment of a particular flow pattern and clot formation prediction.
Topics: Blood Platelets; Humans; Hydrodynamics; Platelet Activation; Stress, Mechanical; Thrombosis
PubMed: 34529037
DOI: 10.1115/1.4052460 -
BioMed Research International 2022Evodia rutaecarpa has multiple pharmacological effects and is widely used in the prevention and treatment of migraine, diabetes, cardiovascular disease, cancer, and...
Evodia rutaecarpa has multiple pharmacological effects and is widely used in the prevention and treatment of migraine, diabetes, cardiovascular disease, cancer, and other chronic diseases; however, the pharmacological effects of its active compound evodiamine (Evo) have not been thoroughly investigated. The purpose of this study was to investigate the effects of Evo on antiplatelet activation and thrombosis. We discovered that Evo effectively inhibited collagen-induced platelet activation but had no effect on platelet aggregation caused by activators such as thrombin, ADP, and U46619. Second, we found that Evo effectively inhibited the release of platelet granules induced by collagen. Finally, evodiamine inhibits the transduction of the SFKs/Syk/Akt/PLC2 activation pathway in platelets. According to in vivo studies, Evo significantly prolonged the mesenteric thromboembolism induced by ferric chloride and had no discernible effect on the coagulation function of mice. In conclusion, the antiplatelet and thrombotic effects of Evo discovered in this study provide an experimental basis for the investigation of the pharmacological mechanisms of Evo and the development of antiplatelet drugs.
Topics: Animals; Blood Platelets; Collagen; Mice; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; Quinazolines; Thrombosis
PubMed: 35937403
DOI: 10.1155/2022/4893859 -
Food & Function Jul 2022Many clinical studies have demonstrated the beneficial effects of black tea on cardiovascular diseases. However, the antiplatelet and antithrombotic activities of...
Many clinical studies have demonstrated the beneficial effects of black tea on cardiovascular diseases. However, the antiplatelet and antithrombotic activities of theaflavin (TF-1) remain unknown. In this study, we aimed to investigate the beneficial effects of TF-1 on platelet activation and thrombosis formation both and . Firstly, the antiplatelet activity of TF-1 was analyzed using platelets isolated from human blood aggregometry, flow cytometry, the ELISA kit, western blot and fluorescence microscopy. Subsequently, the analysis of the hemostatic state and thrombosis formation was carried out in C57BL/6 mice based on the tail bleeding time and an FeCl-induced arterial thrombus model. The results showed that TF-1 could prominently inhibit platelet aggregation in a dose-dependent manner, and attenuate P-selectin expression, fibrinogen binding, spreading and thromboxane A2 (TxA2) formation. Western blot analysis showed that TF-1 potently inhibited spleen tyrosine kinase (Syk) and Akt (ser473/474) phosphorylation. The data further confirmed the inhibition of platelet activation by TF-1 with a prolonged arterial occlusion time (from 15.0 ± 1.1 minutes to 40.0 ± 5.4 minutes). All the results indicated that TF-1 is a powerful inhibitor of platelet activation and thrombosis formation in C57BL/6 mice, and could be developed as a novel food-based inhibitor of thrombotic disorders.
Topics: Animals; Antioxidants; Biflavonoids; Blood Platelets; Catechin; Humans; Mice; Mice, Inbred C57BL; Platelet Activation; Platelet Aggregation; Thrombosis
PubMed: 35815842
DOI: 10.1039/d2fo00152g -
The International Journal of... Dec 2020Platelets are anucleated blood constituents, vital for hemostasis and involved in the pathophysiology of several cardiovascular, neurovascular diseases as well as... (Review)
Review
Platelets are anucleated blood constituents, vital for hemostasis and involved in the pathophysiology of several cardiovascular, neurovascular diseases as well as inflammatory processes and metastasis. Over the past few years, the molecular processes that regulate the function of platelets in hemostasis and thrombosis have emerged revealing platelets to be perhaps more complex than may have been expected. The most understood part of platelets is to respond to a blood vessel injury by altering shape, secreting granule contents, and aggregating. These responses, while advantageous for hemostasis, can become detrimental when they root ischemia or infarction. Only a few transcription and signaling factors involved in platelet biogenesis have been identified till date. Platelets encompass an astonishingly complete array of organelles and storage granules including mitochondria, lysosomes, alpha granules, dense granules, a dense tubular system (analogous to the endoplasmic reticulum of nucleated cells); a highly invaginated plasma membrane system known as the open canalicular system (OCS) and large fields of glycogen. Platelets as a model cells to study neurological disorders have been recommended by several researchers since several counterparts exist between platelets and the brain, which make them interesting for studying the neurobiology of various neurological disorders. This review has been compiled with an aim to integrate the latest research on platelet biogenesis, activation and aggregation focusing on the molecular pathways that power and regulate these processes. The dysregulation of important molecular players affecting fluctuating platelet biology and thereby resulting in neurovascular diseases has also been discussed.
Topics: Blood Platelets; Cerebrovascular Disorders; Humans; Nervous System Diseases; Organelle Biogenesis; Platelet Activation; Platelet Aggregation; Signal Transduction
PubMed: 32069430
DOI: 10.1080/00207454.2020.1732372 -
Biochemical Pharmacology Dec 2021Platelets from septic patients exhibit increased reactivity. However, the underlying mechanism of sepsis-induced platelet hyperactivity is still not completely...
BACKGROUND
Platelets from septic patients exhibit increased reactivity. However, the underlying mechanism of sepsis-induced platelet hyperactivity is still not completely understood.
OBJECTIVE
P2Y is a central receptor for platelet activation. In this study, we investigated the role of platelet P2Y in platelet hyperactivity during sepsis.
METHODS
We measured platelet P2Y expression and aggregation in response to ADP in septic patients and cecal ligation and puncture (CLP)-treated mice. We also detected the downstream signaling of P2Y in resting platelets from patients and mice with sepsis. The role of nucleotide-binding oligomerization domain 2 (NOD2)/RIP2/NF-κB/P65 pathway in sepsis-induced platelet P2Y high expression was also investigated. Finally, we compared the antiplatelet and antithrombotic effects of clopidogrel, prasugrel, and ticagrelor in experimental sepsis in mice and rats.
RESULTS
Compared to healthy subjects, platelets from septic patients exhibit P2Y hyperactivity and higher P2Y expression. pAkt is enhanced and pVASP is impaired in resting platelets from the patients, indicating the constitutive activation of platelet P2Y receptor. Mouse sepsis model recapitulates the findings in septic patients. NOD2 deficiency attenuates sepsis-induced platelet P2Y high expression, hyperactivity, and thrombosis. Prasugrel and ticagrelor are potent P2Y inverse agonists, and exhibit superior antiplatelet and antithrombotic efficacy over clopidogrel in mice and rats with sepsis.
CONCLUSIONS
NOD2 activation upregulates platelet P2Y expression, which is constitutively activated and contributes to platelet hyperactivity in septic status. Compared to clopidogrel, prasugrel and ticagrelor are potent P2Y inverse agonists with superior antiplatelet and antithrombotic efficacy in experimental sepsis.
Topics: Animals; Cell Line; Female; Humans; Male; Megakaryocytes; Mice; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Nod2 Signaling Adaptor Protein; Platelet Activation; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Rats; Rats, Sprague-Dawley; Receptors, Purinergic P2Y12; Sepsis; Thrombosis; Up-Regulation
PubMed: 34748820
DOI: 10.1016/j.bcp.2021.114822 -
International Journal of Molecular... Jul 2020Reactive oxygen species (ROS) and mitochondria play a pivotal role in regulating platelet functions. Platelet activation determines a drastic change in redox balance and... (Review)
Review
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.
Topics: Animals; Apoptosis; Biomarkers; Blood Platelets; Humans; Mitochondria; NADPH Oxidases; Oxidation-Reduction; Platelet Activation; Reactive Oxygen Species; Signal Transduction
PubMed: 32660144
DOI: 10.3390/ijms21144866 -
Pannexin-1 Activation by Phosphorylation Is Crucial for Platelet Aggregation and Thrombus Formation.International Journal of Molecular... May 2022Pannexin-1 (PANX1) is a transmembrane protein that forms ion channels as hexamers on the plasma membrane. Electrophysiological studies prove that PANX1 has a high...
Pannexin-1 (PANX1) is a transmembrane protein that forms ion channels as hexamers on the plasma membrane. Electrophysiological studies prove that PANX1 has a high conductance for adenosine triphosphate (ATP), which plays an important role as a signal molecule in platelet activation. Recently, it was shown that PANX1 channels modulate platelet functions. To date, it remains unclear how PANX1 channels are activated and which signaling mechanisms are responsible for impaired hemostasis and thrombosis. Analysis of PANX1 phosphorylation at Tyr and Tyr, and the impact on platelet activation and thrombus formation using genetically modified platelets or pharmacological inhibitors. Platelet activation via immunoreceptor tyrosine-based activation motif (ITAM) coupled, G Protein-Coupled Receptors (GPCR) and thromboxane receptor (TP)-mediated signaling pathways led to increased PANX1 phosphorylation at Tyr and Tyr. We identified the Src-GPVI signaling axes as the main pathway inducing PANX1 activation, while PKC and Akt play a minor role. PANX1 channels function as ATP release channels in platelets to support arterial thrombus formation. PANX1 activation is regulated by phosphorylation at Tyr and Tyr following platelet activation. These results suggest an important role of PANX1 in hemostasis and thrombosis by releasing extracellular ATP to support thrombus formation.
Topics: Adenosine Triphosphate; Animals; Blood Platelets; Connexins; Humans; Mice; Nerve Tissue Proteins; Phosphorylation; Platelet Activation; Platelet Aggregation; Thrombosis
PubMed: 35563450
DOI: 10.3390/ijms23095059 -
Frontiers in Immunology 2023
Topics: Humans; COVID-19; Platelet Activation
PubMed: 37818358
DOI: 10.3389/fimmu.2023.1285355 -
Hamostaseologie Feb 2021Platelet activation and aggregation are essential to limit blood loss at sites of vascular injury but may also lead to occlusion of diseased vessels. The platelet... (Review)
Review
Platelet activation and aggregation are essential to limit blood loss at sites of vascular injury but may also lead to occlusion of diseased vessels. The platelet cytoskeleton is a critical component for proper hemostatic function. Platelets change their shape after activation and their contractile machinery mediates thrombus stabilization and clot retraction. In vitro studies have shown that platelets, which come into contact with proteins such as fibrinogen, spread and first form filopodia and then lamellipodia, the latter being plate-like protrusions with branched actin filaments. However, the role of platelet lamellipodia in hemostasis and thrombus formation has been unclear until recently. This short review will briefly summarize the recent findings on the contribution of the actin cytoskeleton and lamellipodial structures to platelet function.
Topics: Actins; Blood Platelets; Humans; Platelet Activation; Thrombosis
PubMed: 33588449
DOI: 10.1055/a-1325-0993 -
Circulation Research Jan 2024
Topics: Mitochondrial Dynamics; Blood Platelets; Megakaryocytes; Hemostasis; Platelet Activation
PubMed: 38236952
DOI: 10.1161/CIRCRESAHA.123.323867