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International Journal of Molecular... Apr 2023It is currently believed that plaque complication, with the consequent superimposed thrombosis, is a key factor in the clinical occurrence of acute coronary syndromes... (Review)
Review
It is currently believed that plaque complication, with the consequent superimposed thrombosis, is a key factor in the clinical occurrence of acute coronary syndromes (ACSs). Platelets are major players in this process. Despite the considerable progress made by the new antithrombotic strategies (P2Y12 receptor inhibitors, new oral anticoagulants, thrombin direct inhibitors, etc.) in terms of a reduction in major cardiovascular events, a significant number of patients with previous ACSs treated with these drugs continue to experience events, indicating that the mechanisms of platelet remain largely unknown. In the last decade, our knowledge of platelet pathophysiology has improved. It has been reported that, in response to physiological and pathological stimuli, platelet activation is accompanied by de novo protein synthesis, through a rapid and particularly well-regulated translation of resident mRNAs of megakaryocytic derivation. Although the platelets are anucleate, they indeed contain an important fraction of mRNAs that can be quickly used for protein synthesis following their activation. A better understanding of the pathophysiology of platelet activation and the interaction with the main cellular components of the vascular wall will open up new perspectives in the treatment of the majority of thrombotic disorders, such as ACSs, stroke, and peripheral artery diseases before and after the acute event. In the present review, we will discuss the novel role of noncoding RNAs in modulating platelet function, highlighting the possible implications in activation and aggregation.
Topics: Humans; Blood Platelets; Anticoagulants; Platelet Activation; Hemostasis; Thrombosis; RNA, Untranslated; Acute Coronary Syndrome; Platelet Aggregation Inhibitors; Platelet Aggregation
PubMed: 37108819
DOI: 10.3390/ijms24087650 -
Handbook of Experimental Pharmacology 2012This chapter summarizes current ideas about the intracellular signaling that drives platelet responses to vascular injury. After a brief overview of platelet activation... (Review)
Review
This chapter summarizes current ideas about the intracellular signaling that drives platelet responses to vascular injury. After a brief overview of platelet activation intended to place the signaling pathways into context, the first section considers the early events of platelet activation leading up to integrin activation and platelet aggregation. The focus is on the G protein-mediated events utilized by agonists such as thrombin and ADP, and the tyrosine kinase-based signaling triggered by collagen. The second section considers the events that occur after integrin engagement, some of which are dependent on close physical contact between platelets. A third section addresses the regulatory events that help to avoid unprovoked or excessive platelet activation, after which the final section briefly considers individual variations in platelet reactivity and the role of platelet signaling in the innate immune response and embryonic development.
Topics: Animals; Blood Platelets; Calcium; GTP-Binding Proteins; Humans; Platelet Activation; Platelet Adhesiveness; Signal Transduction
PubMed: 22918727
DOI: 10.1007/978-3-642-29423-5_3 -
Transfusion Medicine Reviews Oct 1998
Review
Topics: Blood Platelets; Humans; Platelet Activation; Platelet Function Tests; Platelet Transfusion
PubMed: 9798270
DOI: 10.1016/s0887-7963(98)80003-5 -
International Journal of Stroke :... Aug 2013An important proportion of transient ischemic attack or ischemic stroke is attributable to moderate or severe (50-99%) atherosclerotic carotid stenosis or occlusion.... (Review)
Review
An important proportion of transient ischemic attack or ischemic stroke is attributable to moderate or severe (50-99%) atherosclerotic carotid stenosis or occlusion. Platelet biomarkers have the potential to improve our understanding of the pathogenesis of vascular events in this patient population. A detailed systematic review was performed to collate all available data on ex vivo platelet activation and platelet function/reactivity in patients with carotid stenosis. Two hundred thirteen potentially relevant articles were initially identified; 26 manuscripts met criteria for inclusion in this systematic review. There was no consistent evidence of clinically informative data from urinary or soluble blood markers of platelet activation in patients with symptomatic moderate or severe carotid stenosis who might be considered suitable for carotid intervention. Data from flow cytometry studies revealed evidence of excessive platelet activation in patients in the early, sub-acute, or late phases after transient ischemic attack or stroke in association with moderate or severe carotid stenosis and in asymptomatic moderate or severe carotid stenosis compared with controls. Furthermore, pilot data suggest that platelet activation may be increased in recently symptomatic than in asymptomatic severe carotid stenosis. Excessive platelet activation and platelet hyperreactivity may play a role in the pathogenesis of first or subsequent transient ischemic attack or stroke in patients with moderate or severe carotid stenosis. Larger longitudinal studies assessing platelet activation status with flow cytometry and platelet function/reactivity in symptomatic vs. asymptomatic carotid stenosis are warranted to improve our understanding of the mechanisms responsible for transient ischemic attack or stroke.
Topics: Animals; Carotid Artery Diseases; Carotid Stenosis; Humans; Platelet Activation
PubMed: 23013536
DOI: 10.1111/j.1747-4949.2012.00866.x -
Biological Chemistry Jul 2013Platelet activation at sites of vascular injury leads to the formation of a hemostatic plug and is crucial for hemostasis. However, uncontrolled platelet activation may... (Review)
Review
Platelet activation at sites of vascular injury leads to the formation of a hemostatic plug and is crucial for hemostasis. However, uncontrolled platelet activation may lead to the formation of occlusive thrombi. Several soluble or matricellular proteins can activate platelets. In this article, we review recent advances in knowledge of the role of galectins in platelet physiology. In soluble or immobilized form, these endogenous glycan-binding proteins trigger platelet activation through the modulation of discrete signaling pathways. We discuss the role of platelet-galectin interactions not only in hemostasis, but also in chronic inflammation, atherosclerosis and cancer.
Topics: Animals; Blood Platelets; Galectins; Hemostasis; Humans; Platelet Activation; Platelet Adhesiveness
PubMed: 23509216
DOI: 10.1515/hsz-2013-0108 -
Platelets Aug 2022During severe sepsis, platelet activation may induce disseminate microvascular thrombosis, which play a key role in critical organ failure. Crucially, most of the...
During severe sepsis, platelet activation may induce disseminate microvascular thrombosis, which play a key role in critical organ failure. Crucially, most of the studies in this field have explored platelet-leukocyte interactions in animal models, or explored platelets under the spectrum of thrombocytopenia or disseminated intravascular coagulation and have not taken into account the complex interplay that might exist between platelets and leukocytes during human septic shock nor the kinetics of platelet activation. Here, we assessed platelet activation parameters at the admission of patients with sepsis to the intensive care unit (ICU) and 48 hours later. Twenty-two patients were enrolled in the study, thirteen (59.1%) of whom were thrombocytopenic. The control group was composed of twelve infection-free patients admitted during the study period. The activation parameters studied included platelet-leukocyte interactions, assessed by flow cytometry in whole blood, as well as membrane surface and soluble platelet activation markers measured by flow cytometry and dedicated ELISA kits. We also investigated platelet aggregation and secretion responses of patients with sepsis following stimulation, compared to controls. At admission, the level of circulating monocyte-platelet and neutrophil-platelet heterotypic aggregates was significantly higher in sepsis patients compared to controls and returned to a level comparable to controls or even below 48 hours later. Basal levels of CD62P and CD63 platelet membrane exposure at admission and 48 hours later were low and similar to controls. In contrast, plasma level of soluble GPVI and soluble CD40 ligand was significantly increased in septic patients, at the two times of analysis, reflecting previous platelet activation. Platelet aggregation and secretion responses induced by specific agonists were significantly decreased in septic conditions, particularly 48 hours after admission. Hence, we have observed for the first time that critically ill septic patients compared to controls have both an early and durable platelet activation while their circulating platelets are less responsive to different agonists.
Topics: Animals; Blood Platelets; Humans; Intensive Care Units; Platelet Activation; Sepsis; Shock, Septic
PubMed: 34915822
DOI: 10.1080/09537104.2021.2007873 -
Blood Cells 1990While the exact nature of the dysfunction of stored platelets is not known, it is generally agreed that the platelet's metabolic activity with lactate accumulation... (Review)
Review
While the exact nature of the dysfunction of stored platelets is not known, it is generally agreed that the platelet's metabolic activity with lactate accumulation presents a significant impediment to prolonged storage. There is an increasing body of evidence that stored platelets have become activated in the preparation and handling of platelet concentrates. Changes in platelet function and structure in concentrates can be explained in terms of sequelae of activation, especially heightened metabolic activity and activation-specific changes in surface glycoproteins on stored platelets. With the use of inhibitors of platelet activation in the preparation of platelet concentrates, the loss of platelet function and integrity is less rapid and platelet metabolic rate is decreased during an extended storage period. Surface levels of glycoprotein Ib, normally decreased during prolonged storage of platelets, are well-preserved in the presence of activation inhibitors. When the use of inhibitors is combined with replacement of plasma with an artificial medium, platelets stored for up to 20 days appear to be metabolically and structurally intact and responsive to stimuli. In summary, platelet activation appears to play a major role in the generation of the storage lesion in platelet concentrates.
Topics: Blood Preservation; Humans; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Membrane Glycoproteins
PubMed: 2190643
DOI: No ID Found -
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 -
Current Pharmaceutical Design 2018Coronary artery disease (CAD) is a disease progressing over many years. Genetic factors, as well as the exposure to risk factors, are continuously leading to endothelial... (Review)
Review
BACKGROUND
Coronary artery disease (CAD) is a disease progressing over many years. Genetic factors, as well as the exposure to risk factors, are continuously leading to endothelial dysfunction, vascular alterations and, eventually, organ damage, major cardiovascular events and deaths. Oxidative stress, platelet hyperactivity and low-grade inflammation are important modulators in this context, contributing to plaque formation. Since platelet activation plays a critical role in the development and progression of atherothrombotic events, the inhibition of platelet hyperactivity may contribute to decreased atherothrombotic risk. The consumption of bioactive foods, and plant-derived polyphenols in particular, might impart anti-thrombotic and cardiovascular protective effects.
METHODS
Aim of this work is to focus on the potential of dietary derived polyphenols to reduce platelet hyperactivity or hypercoagulability in addition to discussing their possible complementary anti-platelet therapeutic potential. All the relevant publications on this topic were systematically reviewed.
RESULTS
Various studies demonstrated that polyphenol supplementation affects platelet aggregation and function in vitro and in vivo, mainly neutralizing free radicals, inhibiting platelet activation and related signal transduction pathways, blocking thromboxane A2 receptors and enhancing nitric oxide production. Experimental data concerning the effect of dietary polyphenols on platelet aggregation in vivo are poor, and results are often conflicting. Only flavanols clearly mirrored in vivo showed the efficacy in vitro in modulating platelet function.
CONCLUSION
Dietary polyphenols, and above all flavanols contained in cocoa and berries, reduce platelet activation and aggregation via multiple pathways. However, more controlled interventional studies are required to establish which doses are required as well as what circulating concentrations are sufficient to induce functional antiplatelet effects.
Topics: Animals; Dietary Supplements; Humans; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Polyphenols
PubMed: 29119922
DOI: 10.2174/1381612823666171109104600 -
Platelets 2013Platelets play a fundamental role in hemostasis. Their functional responses have to be tightly controlled as any disturbance may lead to bleeding disorders or... (Review)
Review
Platelets play a fundamental role in hemostasis. Their functional responses have to be tightly controlled as any disturbance may lead to bleeding disorders or thrombosis. It is thus important to clearly identify and understand the signaling mechanisms involved in platelet function. An important role of c-Cbl and Cbl-b ubiquitin ligases in platelet functional responses and in hematological malignancies has been recently described. Cbl proteins perform negative and positive regulation of several signaling pathways in platelets. In this review, we explore the role of Cbl proteins in platelet functional responses.
Topics: Blood Platelets; Humans; Platelet Activation; Proto-Oncogene Proteins c-cbl
PubMed: 22931288
DOI: 10.3109/09537104.2012.715216