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BioMed Research International 2021Statins are a class of drugs widely used in clinical practice for their lipid-lowering and pleiotropic effects. In recent years, a correlation between statins and... (Review)
Review
PURPOSE
Statins are a class of drugs widely used in clinical practice for their lipid-lowering and pleiotropic effects. In recent years, a correlation between statins and platelet function has been unveiled in the literature that might introduce new therapeutic indications for this class of drugs. This review is aimed at summarizing the mechanisms underlying statin-platelet interaction in the cardiologic scenario and building the basis for future in-depth studies.
METHODS
We conducted a literature search through PubMed, Embase, EBSCO, Cochrane Database of Systematic Reviews, and Web of Science from their inception to June 2020.
RESULTS
Many pathways could explain the interaction between statins and platelets, but the specific effect depends on the specific compound. Some could be mediated by enzymes that allow the entry of drugs into the cell (OATP2B1) and others by enzymes that mediate their activation (PLA2, MAPK, TAX2, PPARs, AKT, and COX-1), recruitment and adhesion (LOX-1, CD36, and CD40L), or apoptosis (BCL2). Statins also appear to have a synergistic effect with aspirin and low molecular weight heparins. Surprisingly, they seem to have an antagonistic effect with clopidogrel.
CONCLUSION
There are many pathways potentially responsible for the interactions between statins and platelets. Their effect appears to be closely related, and each single effect can be barely measured. Also, the same compound might have complex downstream signaling with potentially opposite effects, i.e., beneficial or deleterious. The multiple clinical implications that can be derived as a result of this interaction, however, represent an excellent reason to develop future in-depth studies.
Topics: Aspirin; Blood Platelets; CD36 Antigens; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Organic Anion Transporters; Platelet Activation; Signal Transduction
PubMed: 33564680
DOI: 10.1155/2021/6661847 -
Current Pharmaceutical Design 2019Platelets are typically recognized for their roles in the maintenance of hemostasis and vascular wall repair to reduce blood loss. Beyond hemostasis, platelets also play... (Review)
Review
Platelets are typically recognized for their roles in the maintenance of hemostasis and vascular wall repair to reduce blood loss. Beyond hemostasis, platelets also play a critical role in pathophysiological conditions like atherosclerosis, stroke, thrombosis, and infections. During infection, platelets interact directly and indirectly with bacteria through a wide range of cellular and molecular mechanisms. Platelet surface receptors such as GPIbα, FcγRIIA, GPIIbIIIa, and TLRs, etc. facilitate direct interaction with bacterial cells. Besides, the indirect interaction between platelet and bacteria involves host plasma proteins such as von Willebrand Factor (vWF), fibronectin, IgG, and fibrinogen. Bacterial cells induce platelet activation, aggregation, and thrombus formation in the microvasculature. The activated platelets induce the Neutrophil Extracellular Traps (NETs) formation, which further contribute to thrombosis. Thus, platelets are extensively anticipated as vital immune modulator cells during infection, which may further lead to cardiovascular complications. In this review, we cover the interaction mechanisms between platelets and bacteria that may lead to the development of thrombotic disorders. Platelet receptors and other host molecules involved in such interactions can be used to develop new therapeutic strategies to combat against infection-induced cardiovascular complications. In addition, we highlight other receptor and enzyme targets that may further reduce infection-induced platelet activation and various pathological conditions.
Topics: Bacteria; Blood Platelets; Extracellular Traps; Hemostasis; Host-Pathogen Interactions; Humans; Platelet Activation; Platelet Aggregation; Thrombosis
PubMed: 31553286
DOI: 10.2174/1381612825666190925163347 -
International Journal of Molecular... Apr 2018Cancer patients experience a four-fold increase in thrombosis risk, indicating that cancer development and progression are associated with platelet activation. Xenograft... (Review)
Review
Cancer patients experience a four-fold increase in thrombosis risk, indicating that cancer development and progression are associated with platelet activation. Xenograft experiments and transgenic mouse models further demonstrate that platelet activation and platelet-cancer cell interaction are crucial for cancer metastasis. Direct or indirect interaction of platelets induces cancer cell plasticity and enhances survival and extravasation of circulating cancer cells during dissemination. In vivo and in vitro experiments also demonstrate that cancer cells induce platelet aggregation, suggesting that platelet-cancer interaction is bidirectional. Therefore, understanding how platelets crosstalk with cancer cells may identify potential strategies to inhibit cancer metastasis and to reduce cancer-related thrombosis. Here, we discuss the potential function of platelets in regulating cancer progression and summarize the factors and signaling pathways that mediate the cancer cell-platelet interaction.
Topics: Biomarkers, Tumor; Blood Platelets; Humans; Models, Biological; Neoplasm Metastasis; Neoplasms; Platelet Activation
PubMed: 29677116
DOI: 10.3390/ijms19041246 -
Journal of Internal Medicine Jul 2024Platelet hyperreactivity and hyperlipidaemia contribute significantly to atherosclerosis. Thus, it is desirable to review the platelet-hyperlipidaemia interplay and its... (Review)
Review
Platelet hyperreactivity and hyperlipidaemia contribute significantly to atherosclerosis. Thus, it is desirable to review the platelet-hyperlipidaemia interplay and its impact on atherogenesis. Native low-density lipoprotein (nLDL) and oxidized LDL (oxLDL) are the key proatherosclerotic components of hyperlipidaemia. nLDL binds to the platelet-specific LDL receptor (LDLR) ApoE-R2', whereas oxLDL binds to the platelet-expressed scavenger receptor CD36, lectin-type oxidized LDLR 1 and scavenger receptor class A 1. Ligation of nLDL/oxLDL induces mild platelet activation and may prime platelets for other platelet agonists. Platelets, in turn, can modulate lipoprotein metabolisms. Platelets contribute to LDL oxidation by enhancing the production of reactive oxygen species and LDLR degradation via proprotein convertase subtilisin/kexin type 9 release. Platelet-released platelet factor 4 and transforming growth factor β modulate LDL uptake and foam cell formation. Thus, platelet dysfunction and hyperlipidaemia work in concert to aggravate atherogenesis. Hypolipidemic drugs modulate platelet function, whereas antiplatelet drugs influence lipid metabolism. The research prospects of the platelet-hyperlipidaemia interplay in atherosclerosis are also discussed.
Topics: Humans; Atherosclerosis; Hyperlipidemias; Blood Platelets; Lipoproteins, LDL; Platelet Activation; Receptors, LDL; Hypolipidemic Agents
PubMed: 38704820
DOI: 10.1111/joim.13794 -
PloS One 2021Galectin-1 (gal-1) is a carbohydrate-binding lectin with important functions in angiogenesis, immune response, hemostasis and inflammation. Comparable functions are...
Galectin-1 (gal-1) is a carbohydrate-binding lectin with important functions in angiogenesis, immune response, hemostasis and inflammation. Comparable functions are exerted by platelet factor 4 (CXCL4), a chemokine stored in the α-granules of platelets. Previously, gal-1 was found to activate platelets through integrin αIIbβ3. Both gal-1 and CXCL4 have high affinities for polysaccharides, and thus may mutually influence their functions. The aim of this study was to investigate a possible synergism of gal-1 and CXCL4 in platelet activation. Platelets were treated with increasing concentrations of gal-1, CXCL4 or both, and aggregation, integrin activation, P-selectin and phosphatidyl serine (PS) exposure were determined by light transmission aggregometry and by flow cytometry. To investigate the influence of cell surface sialic acid, platelets were treated with neuraminidase prior to stimulation. Gal-1 and CXCL4 were found to colocalize on the platelet surface. Stimulation with gal-1 led to integrin αIIbβ3 activation and to robust platelet aggregation, while CXCL4 weakly triggered aggregation and primarily induced P-selectin expression. Co-incubation of gal-1 and CXCL4 potentiated platelet aggregation compared with gal-1 alone. Whereas neither gal-1 and CXCL4 induced PS-exposure on platelets, prior removal of surface sialic acid strongly potentiated PS exposure. In addition, neuraminidase treatment increased the binding of gal-1 to platelets and lowered the activation threshold for gal-1. However, CXCL4 did not affect binding of gal-1 to platelets. Taken together, stimulation of platelets with gal-1 and CXCL4 led to distinct and complementary activation profiles, with additive rather than synergistic effects.
Topics: Blood Platelets; Galectin 1; Humans; N-Acetylneuraminic Acid; Platelet Activation; Platelet Aggregation; Platelet Factor 4; Platelet Glycoprotein GPIIb-IIIa Complex; Signal Transduction
PubMed: 33411760
DOI: 10.1371/journal.pone.0244736 -
Interventional Cardiology Clinics Jan 2017Hemostasis requires tightly regulated interaction of the coagulation system, platelets, blood cells, and vessel wall components at a site of vascular injury.... (Review)
Review
Hemostasis requires tightly regulated interaction of the coagulation system, platelets, blood cells, and vessel wall components at a site of vascular injury. Dysregulation of this response may result in excessive bleeding if the response is impaired, and pathologic thrombosis with vessel occlusion and tissue ischemia if the response is robust. Studies have elucidated the major molecular signaling pathways responsible for platelet activation and aggregation. Antithrombotic agents targeting these pathways are in clinical use. This review summarizes research examining mechanisms by which these multiple platelet signaling pathways are integrated at a site of vascular injury to produce an optimal hemostatic response.
Topics: Animals; Blood Coagulation; Blood Platelets; Humans; Platelet Activation; Platelet Aggregation; Thrombosis; Vascular System Injuries
PubMed: 27886814
DOI: 10.1016/j.iccl.2016.08.001 -
BioMed Research International 2015As platelet activation is closely related to the liberation of growth factors and inflammatory mediators, platelets play a central role in the development of CVD.... (Review)
Review
As platelet activation is closely related to the liberation of growth factors and inflammatory mediators, platelets play a central role in the development of CVD. Virtually all cardiovascular risk factors favor platelet hyperreactivity and, accordingly, also physical (in)activity affects platelet function. Within this paper, we will summarize and discuss the current knowledge on the impact of acute and habitual exercise on platelet function. Although there are apparent discrepancies regarding the reported effects of acute, strenuous exercise on platelet activation, a deeper analysis of the available literature reveals that the applied exercise intensity and the subjects' cardiorespiratory fitness represent critical determinants for the observed effects. Consideration of these factors leads to the summary that (i) acute, strenuous exercise can lead to platelet activation, (ii) regular physical activity and/or physical fitness diminish or prevent platelet activation in response to acute exercise, and (iii) habitual physical activity and/or physical fitness also favorably modulate platelet function at physical rest. Notably, these effects of exercise on platelet function show obvious similarities to the well-recognized relation between exercise and the risk for cardiovascular events where vigorous exercise transiently increases the risk for myocardial infarction and a physically active lifestyle dramatically reduces cardiovascular mortality.
Topics: Blood Platelets; Cardiovascular Diseases; Humans; Motor Activity; Platelet Activation; Platelet Aggregation; Risk Factors; Sedentary Behavior
PubMed: 26557653
DOI: 10.1155/2015/165078 -
Future Medicinal Chemistry Jun 2017Antiplatelet therapy displays a critical role in the treatment and prevention of antithrombotic disorders. Many new antiplatelet agents have been developed following the... (Review)
Review
Antiplatelet therapy displays a critical role in the treatment and prevention of antithrombotic disorders. Many new antiplatelet agents have been developed following the emergence of various clinical limitations of classical antiplatelet drugs. This review covers mainly the recent advances in the development of P2Y antagonists and GPIIb/IIIa antagonists. Meanwhile, it summarizes promising approaches to new platelet surface receptors such as prostanoid EP3 receptor, thromboxane A prostanoid receptor, protease-activated receptors, GPIb-IX-V receptor and P-selectin. In addition, PI3K, a critical protein at the inside signaling pathway of platelet activation is also mentioned as an important antiplatelet target. Moreover, the development of respective drug candidates is discussed in detail.
Topics: Blood Platelets; Humans; Molecular Structure; Platelet Activation; Platelet Aggregation Inhibitors
PubMed: 28632424
DOI: 10.4155/fmc-2017-0001 -
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