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Cardiovascular Toxicology Feb 2020Globally, one of the major causes of death is the cardiovascular disease (CVD), and platelets play an important role in thrombosis and atherosclerosis that led to death.... (Review)
Review
Globally, one of the major causes of death is the cardiovascular disease (CVD), and platelets play an important role in thrombosis and atherosclerosis that led to death. Platelet activation can be done by different molecules, genes, pathways, and chemokines. Lipids activate platelets by inflammatory factors, and platelets are activated by receptors of peptide hormones, signaling and secreted proteins, microRNAs (miRNAs), and oxidative stress which also affect the platelet activation in older age. In addition, surface molecules on platelets can interact with other cells and chemokines in activated platelets and cause inflammation thrombosis events and CVD. However, these molecules activating platelets or being activated by platelets can be suggested as the markers to predict the clinical outcome of CVD and can be targeted to reduce thrombosis and atherosclerosis. However, hindering these molecules by other factors such as genes and receptors can reduce platelet activation and aggregation and targeting these molecules can control platelet interactions, thrombosis, and CVD. In addition, dual therapy with the receptor blockers and novel drugs results in better management of CVD patients. Overall, our review will emphasize on the molecules involved in the activation of platelets and on the molecules that are activated by platelets in CVD and discuss the molecules that can be blocked or targeted to reduce the thrombosis events and control CVD.
Topics: Animals; Blood Platelets; Cardiovascular Diseases; Humans; Molecular Targeted Therapy; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; Signal Transduction
PubMed: 31784932
DOI: 10.1007/s12012-019-09555-4 -
Blood Reviews Sep 1995This review article describes the different receptors, second-messengers and mechanisms involved in platelet activation. Several platelet agonists have well-defined... (Review)
Review
This review article describes the different receptors, second-messengers and mechanisms involved in platelet activation. Several platelet agonists have well-defined receptors at the platelet membrane of which a number are single polypeptides with 7 hydrophobic transmembrane domains. These receptors are connected, via GTP regulatory proteins, with cytoplasmic second-messenger-generating enzymes. Phospholipase C and adenylate cyclase are the two best-known enzymes, generating inositol triphosphate (IP3) and diacyl glycerol from phosphatidylinositol biphosphate and cyclic AMP from ATP respectively. The intraplatelet free calcium level, which is critical for the activation status of the platelet, is increased by IP3 and is lowered in the presence of rising cyclic AMP concentrations. Shape-change occurs with small increases in intraplatelet calcium, while aggregation and secretion of granules take place at higher calcium, levels. The role of myosin and actin filaments and of transmembrane glycoproteins is further discussed.
Topics: Animals; Blood Platelets; Cell Size; Humans; Platelet Activation; Platelet Adhesiveness; Platelet Aggregation; Receptors, Cell Surface; Second Messenger Systems
PubMed: 8563516
DOI: 10.1016/0268-960x(95)90020-9 -
Cardiovascular & Hematological... 2018Ischemia is a multifactorial disorder in which several genetic and environmental factors are involved. Platelets are the major causative agents of this disease because... (Review)
Review
BACKGROUND
Ischemia is a multifactorial disorder in which several genetic and environmental factors are involved. Platelets are the major causative agents of this disease because their elevated activity and aggregation would increase the risk of atherosclerosis and thrombosis, as well as ischemia. A number of polymorphisms in platelet receptors can increase the risk of ischemia and single-nucleotide polymorphisms (SNPs) have been detected in platelets. In addition, polymorphisms in other genes have been shown to cause platelet adhesion and aggregation that plays a role in ischemia. Patients respond differently to anti-platelet drugs which are used to treat patients with ischemia. Polymorphisms affect patients' responses to anti-platelet drugs, for instance, by increasing platelet activity and causing resistance of platelets to these drugs. Diagnosis of these polymorphisms can greatly contribute to better prediction of prognosis and response to treatment of patients, leading to more effective therapeutic strategies and a proper approach to ischemia.
CONCLUSION
In this review, we have evaluated the role of polymorphisms involved in platelet activation and development of ischemia.
Topics: Atherosclerosis; Blood Platelets; Humans; Ischemia; Platelet Activation; Platelet Aggregation
PubMed: 29577867
DOI: 10.2174/1871529X18666180326121239 -
Blood Reviews Sep 2019Platelets play a major role in primary hemostasis and thrombus formation. After vascular injury, platelets adhere to injured site and rapidly change their shape that... (Review)
Review
Platelets play a major role in primary hemostasis and thrombus formation. After vascular injury, platelets adhere to injured site and rapidly change their shape that switches the resting platelets to active state. Activated platelets aggregate and secrete biologically active intermediate substances that further potentiate platelet activation through autocrine as well as paracrine mechanisms. The activated platelet expresses certain proteins that are not seen on the resting platelets, thus these proteins serve as markers of platelet activation. Other subsequent events of platelet activation include release of microvesicles and formation of complexes with other circulating cells, like monocytes and neutrophils. Platelet activation markers are useful tools in evaluating risk factors of thrombosis in a variety of clinical conditions. Increased platelet activation has been associated with various pathological conditions such as acute coronary syndrome, stroke, peripheral vascular disease and other inflammatory diseases. The advancement in technologies helps in determining the status of platelet activation in such clinical conditions. This article focuses on the sources, mechanism and diagnosis of platelet activation and their clinical implications.
Topics: Humans; Platelet Activation; Risk Factors; Thrombosis
PubMed: 31133440
DOI: 10.1016/j.blre.2019.05.007 -
Comprehensive Physiology Jun 2018This overview article for the Comprehensive Physiology collection is focused on detailing platelets, how platelets respond to various stimuli, how platelets interact... (Review)
Review
This overview article for the Comprehensive Physiology collection is focused on detailing platelets, how platelets respond to various stimuli, how platelets interact with their external biochemical environment, and the role of platelets in physiological and pathological processes. Specifically, we will discuss the four major functions of platelets: activation, adhesion, aggregation, and inflammation. We will extend this discussion to include various mechanisms that can induce these functional changes and a discussion of some of the salient receptors that are responsible for platelets interacting with their external environment. We will finish with a discussion of how platelets interact with their vascular environment, with a special focus on interactions with the extracellular matrix and endothelial cells, and finally how platelets can aid and possibly initiate the progression of various vascular diseases. Throughout this overview, we will highlight both the historical investigations into the role of platelets in health and disease as well as some of the more current work. Overall, the authors aim for the readers to gain an appreciation for the complexity of platelet functions and the multifaceted role of platelets in the vascular system. © 2017 American Physiological Society. Compr Physiol 8:1117-1156, 2018.
Topics: Animals; Blood Platelets; Humans; Platelet Activation; Platelet Adhesiveness; Vascular Remodeling
PubMed: 29978900
DOI: 10.1002/cphy.c170049 -
Microbiology Spectrum Dec 2022Streptococcus bovisStreptococcus equinus complex (SBSEC) is a common cause of infective endocarditis (IE). For IE-pathogens, the capacity to activate and aggregate...
Streptococcus bovisStreptococcus equinus complex (SBSEC) is a common cause of infective endocarditis (IE). For IE-pathogens, the capacity to activate and aggregate platelets is believed to be an important virulence mechanism. While the interactions between bacteria and platelets have been described in detail for many Gram-positive pathogens, little research has been carried out with SBSEC in this respect. Twenty-six isolates of the four most common species and subspecies of SBSEC identified in bacteremia were collected, and interactions with platelets were investigated in platelet rich plasma (PRP) from three donors. Aggregation was studied using light-transmission aggregometry and platelet activation using flow cytometry detecting surface upregulation of CD62P. Platelets and serum were treated with different inhibitors to determine mechanisms involved in platelet aggregation and activation. Twenty-two of 26 isolates induced aggregation in at least one donor, and four isolates induced aggregation in all three donors. In PRP from donor 1, isolate SL1 induced a rapid aggregation with a median time of 70 s to reach 50% aggregation. Blockade of the platelet Fc-receptor or enzymatic cleavage of IgG abolished platelet activation and aggregation. The capacity for bacteria-induced platelet aggregation was also shown to be transferable between donors through serum. SBSEC mediates platelet aggregation in an IgG and IgG-Fc-receptor dependent manner. Bacterial activation of platelets through this pathway is common for many bacteria causing IE and could be a potential therapeutic target for the prevention and treatment of this infection. The capacity of bacteria to activate and aggregate platelets is believed to contribute to the pathogenesis of IE. The Streptococcus bovis/Streptococcus equinus complex (SBSEC) contains known IE-pathogens, but there is limited research on the different subspecies ability to interact with platelets and what signaling pathways are involved. This study reports that 22 of 26 tested isolates of different subspecies within SBSEC can induce aggregation, and that aggregation is host dependent. The Fc-IgG-receptor pathway was shown essential for platelet activation and aggregation. To the best of our knowledge, this is the first study that reports on platelet interactions of SBSEC-isolates other than Streptococcus gallolyticus subspecies as well as the first study to report of mechanisms of platelet interaction of SBSEC-isolates. It adds SBSEC to a group of bacteria that activate and aggregate platelets via the platelet Fc-receptor. This could be a potential therapeutic target for prevention of IE.
Topics: Streptococcus bovis; Platelet Activation; Platelet Aggregation; Blood Platelets; Immunoglobulin G
PubMed: 36374116
DOI: 10.1128/spectrum.01861-22 -
Seminars in Thrombosis and Hemostasis Apr 2016Platelets are the smallest blood cells, numbering 150 to 350 × 10(9)/L in healthy individuals. The ability of activated platelets to adhere to an injured vessel... (Review)
Review
Platelets are the smallest blood cells, numbering 150 to 350 × 10(9)/L in healthy individuals. The ability of activated platelets to adhere to an injured vessel wall and form aggregates was first described in the 19th century. Besides their long-established roles in thrombosis and hemostasis, platelets are increasingly recognized as pivotal players in numerous other pathophysiological processes including inflammation and atherogenesis, antimicrobial host defense, and tumor growth and metastasis. Consequently, profound knowledge of platelet structure and function is becoming more important in research and in many fields of modern medicine. This review provides an overview of platelet physiology focusing particularly on the structure, granules, surface glycoproteins, and activation pathways of platelets.
Topics: Blood Platelets; Hemostasis; Humans; Models, Biological; Platelet Activation; Platelet Adhesiveness; Platelet Aggregation; Platelet Membrane Glycoproteins; Signal Transduction; Thrombosis
PubMed: 26926581
DOI: 10.1055/s-0035-1564835 -
Platelets Feb 2022Influenza infection has long been associated with prothrombotic outcomes in patients and platelets are the blood component predominantly responsible for thrombosis. In... (Review)
Review
Influenza infection has long been associated with prothrombotic outcomes in patients and platelets are the blood component predominantly responsible for thrombosis. In this review, we outline what is known about influenza interaction with human platelets, virion internalization, and viral RNA sensing, and the consequent impact on platelet function. We further discuss activation of platelets by IgG-influenza complexes and touch upon mechanisms of environmental platelet activation that relate to prothrombotic outcomes in patients during infection.
Topics: Blood Platelets; Humans; Influenza, Human; Platelet Activation
PubMed: 34369285
DOI: 10.1080/09537104.2021.1961710 -
Haemostasis Oct 1996Work on growth factor receptors in other cells has led to the concept that tyrosine phosphorylation of receptor cytoplasmic domains leads to recruitment of signaling... (Review)
Review
Work on growth factor receptors in other cells has led to the concept that tyrosine phosphorylation of receptor cytoplasmic domains leads to recruitment of signaling molecules to appropriate sub-membrane locations. Complexes of molecules are assembled through structural motifs that mediate phosphotyrosine-SH2 domain and SH3-proline-rich domain interactions. These interactions lead to activation of signaling molecules, especially activation of members of the Ras superfamily that in turn mediate downstream effects on gene regulation, vesicle movement, and cytoskeletal reorganizations. In platelets, signaling occurs primarily through members of the seven transmembrane-hererotrimeric G-protein coupled family of receptors and through adhesion receptors. The most rapid are of growth in recent years has been the realization that signaling through both G-protein coupled receptors and adhesion receptors is dependent on tyrosine kinase activation, recruitment of complexes of SH2, SH3, and proline-rich signaling molecules to appropriate locations in the cell, and on activation of members of the Ras superfamily of proteins. Because neither G-protein coupled receptors nor adhesion receptors have intrinsic tyrosine kinase activity, mechanisms presumably exist for using non-receptor kinases to initiate tyrosine phosphorylation reactions that in turn lead to the recruitment of signaling molecules. As discussed in this article, many tyrosine kinases exist in platelets and some of these are known to be tyrosine phosphorylated and activated following platelet activation. The theme that is emerging is that these tyrosine kinases may serve to phosphorylate submembranous proteins including receptors for cytoplasmic domains or components of the submembranous cytoskeleton of adhesion-receptor cytoskeleton complexes that can then recruit and activate appropriate signaling molecules. The challenge in future years will be to identity the way in which the activation of tyrosine kinase(s) is induced by receptor activation, identify the tyrosine kinase(s) involved, and identify the way in which specific members of the Ras superfamily activate downstream effectors to induce the responses of platelets to activation.
Topics: Animals; Endothelium, Vascular; GTP-Binding Proteins; Humans; Integrins; Models, Biological; Multigene Family; Phosphorylation; Platelet Activation; Platelet Adhesiveness; Platelet Membrane Glycoproteins; Protein Processing, Post-Translational; Protein-Tyrosine Kinases; Signal Transduction; ras Proteins; src Homology Domains
PubMed: 8979117
DOI: 10.1159/000217291 -
Thrombosis and Haemostasis Aug 2002Platelet activation and blood coagulation are complementary, mutually dependent processes in haemostasis and thrombosis. Platelets interact with several coagulation... (Review)
Review
Platelet activation and blood coagulation are complementary, mutually dependent processes in haemostasis and thrombosis. Platelets interact with several coagulation factors, while the coagulation product thrombin is a potent platelet-activating agonist. Activated platelets come in a procoagulant state after a prolonged elevation in cytosolic [Ca2+]i. Such platelets, e.g. when adhering to collagen via glycoprotein VI, expose phosphatidylserine (PS) at their outer surface and produce (PS-exposing) membrane blebs and microvesicles. Inhibition of aminophospholipid translocase and activation of phospholipid scramblase mediate the exposure of PS, whereas calpain-mediated protein cleavage leads to membrane blebbing and vesiculation. Surface-exposed PS strongly propagates the coagulation process by facilitating the assembly and activation of tenase and prothrombinase complexes. Factor IXa and platelet-bound factor Va support these activities. In addition, platelets can support the initiation phase of coagulation by providing binding sites for prothrombin and factor XI. They thereby take over the initiating role of tissue factor and factor VIIa in coagulation activation.
Topics: Blood Coagulation; Blood Coagulation Factors; Humans; Membrane Lipids; Platelet Activation; Signal Transduction
PubMed: 12195687
DOI: No ID Found