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International Journal of Molecular... Aug 2023COVID-19 has been a diagnostic and therapeutic challenge. It has marked a paradigm shift when considering other types of pneumonia etiology. We analyzed the biomarkers...
COVID-19 has been a diagnostic and therapeutic challenge. It has marked a paradigm shift when considering other types of pneumonia etiology. We analyzed the biomarkers related to endothelial damage and immunothrombosis in COVID-19 in comparison to community-acquired pneumonia (CAP) through a case-control study of 358 patients with pneumonia (179 hospitalized with COVID-19 vs. 179 matched hospitalized with CAP). Endothelial damage markers (endothelin and proadrenomedullin), neutrophil extracellular traps (NETs) (citrullinated-3 histone, cell-free DNA), and platelet activation (soluble P-selectin) were measured. In-hospital and 1-year follow-up outcomes were evaluated. Endothelial damage, platelet activation, and NET biomarkers are significantly higher in CAP compared to COVID-19. In-hospital mortality in COVID-19 was higher compared to CAP whereas 1-year mortality and cardiovascular complications were higher in CAP. In the univariate analysis (OR 95% CIs), proADM and endothelin were associated with in-hospital mortality (proADM: CAP 3.210 [1.698-6.070], COVID-19 8.977 [3.413-23.609]; endothelin: CAP 1.014 [1.006-1.022], COVID-19 1.024 [1.014-1.034]), in-hospital CVE (proADM: CAP 1.623 [1.080-2.439], COVID-19 2.146 [1.186-3.882]; endothelin: CAP 1.005 [1.000-1.010], COVID-19 1.010 [1.003-1.018]), and 1-year mortality (proADM: CAP 2.590 [1.644-4.080], COVID-19 13.562 [4.872-37.751]; endothelin: CAP 1.008 [1.003-1.013], COVID-19 1.026 [1.016-1.037]). In conclusion, COVID-19 and CAP showed different expressions of endothelial damage and NETs. ProADM and endothelin are associated with short- and long-term mortality.
Topics: Humans; COVID-19; Case-Control Studies; Extracellular Traps; Pneumonia; Platelet Activation; Community-Acquired Infections
PubMed: 37686001
DOI: 10.3390/ijms241713194 -
Phytomedicine : International Journal... Jan 2023Cardiovascular disease is one of the most concerning chronic diseases in the world. Many studies have shown that platelet overactivation is a very important factor in...
BACKGROUND
Cardiovascular disease is one of the most concerning chronic diseases in the world. Many studies have shown that platelet overactivation is a very important factor in the occurrence and development of cardiovascular diseases. At present, the widely used antiplatelet drugs have some defects, such as drug resistance and adverse reactions.
PURPOSE
The purpose of this article is to summarize the main mechanisms and pathways of platelet activation, the main targets of antiplatelet aggregation, and the antiplatelet aggregation components of natural drugs and their mechanisms of action to provide new research ideas for the development and application of antiplatelet drugs.
STUDY DESIGN AND METHODS
In this review, we systematically searched the PubMed, Google Scholar, Web of Science, and CNKI databases and selected studies based on predefined eligibility criteria. We then assessed their quality and extracted data.
RESULTS
ADP, AA, THR, AF, collagen, SDF-1α, and Ca can induce platelet aggregation and trigger thrombosis. Natural drugs have a good inhibitory effect on platelet activation. More than 50 kinds of natural drugs and over 120 kinds of chemical compounds, including flavonoids, alkaloids, saponins, terpenoids, coumarins, and organic acids, have significantly inhibited platelet activation activity. The MAPK pathway, cGMP-PKG pathway, cAMP-PKA pathway, PI3K-AKT pathway, PTK pathway, PLC pathway, and AA pathway are the main mechanisms and pathways of platelet activation.
CONCLUSION
Natural drugs and their active ingredients have shown good activity and application prospects in anti-platelet aggregation. We hope that this review provides new research ideas for the development and application of antiplatelet drugs.
Topics: Humans; Platelet Aggregation Inhibitors; Phosphatidylinositol 3-Kinases; Platelet Activation; Platelet Aggregation; Blood Platelets; Cardiovascular Diseases
PubMed: 36347177
DOI: 10.1016/j.phymed.2022.154463 -
International Journal of Molecular... Oct 2021Upon activation, maternal platelets provide a source of proinflammatory mediators in the intervillous space of the placenta. Therefore, platelet-derived factors may... (Review)
Review
Upon activation, maternal platelets provide a source of proinflammatory mediators in the intervillous space of the placenta. Therefore, platelet-derived factors may interfere with different trophoblast subtypes of the developing human placenta and might cause altered hormone secretion and placental dysfunction later on in pregnancy. Increased platelet activation, and the subsequent occurrence of placental fibrinoid deposition, are linked to placenta pathologies such as preeclampsia. The composition and release of platelet-derived factors change over gestation and provide a potential source of predicting biomarkers for the developing fetus and the mother. This review indicates possible mechanisms of platelet-trophoblast interactions and discusses the effect of increased platelet activation on placenta development.
Topics: Animals; Biomarkers; Blood Platelets; Cell Communication; Disease Susceptibility; Epithelial Cells; Female; Humans; Maternal-Fetal Exchange; Placenta; Platelet Activation; Pregnancy; Pregnancy Complications; Trophoblasts
PubMed: 34639070
DOI: 10.3390/ijms221910732 -
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 -
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 -
Gas plasma-induced platelet activation corresponds to reactive species profiles and lipid oxidation.Free Radical Biology & Medicine Oct 2023Surgical-induced hemostasis is a critical step in the closure of incisions, which is frequently achieved via electrocauterization and subsequent tissue necrotization....
Surgical-induced hemostasis is a critical step in the closure of incisions, which is frequently achieved via electrocauterization and subsequent tissue necrotization. The latter is associated with postoperative complications. Recent in vivo work suggested reactive species-producing gas plasma technology as a pro-homeostatic agent acting via platelet activation. However, it remained elusive how platelet activation is linked to lipid and protein oxidation and the reactive species compositions. A direct relation between the reactive species composition and platelet activation was revealed by assessing the production of several reactive species and by using antioxidants. In addition, platelet lipidome and proteome analysis identified significantly regulated key lipids in the platelet activation pathway, such as diacylglycerols and phosphatidylinositol as well as oxylipins like thromboxanes. Lipid oxidation products mainly derived from phosphatidylethanolamine and phosphatidylserine species were observed at modest levels. In addition, oxidative post-translational modifications were identified on key proteins of the hemostasis machinery. This study provides new insights into oxidation-induced platelet activation in general and suggests a potential role of those processes in gas plasma-mediated hemostasis in particular.
Topics: Platelet Activation; Blood Platelets; Oxidation-Reduction; Antioxidants; Lipids
PubMed: 37490986
DOI: 10.1016/j.freeradbiomed.2023.07.024 -
Journal of Thrombosis and Haemostasis :... Oct 2021Platelets are now recognized as immunological sentries in the first line of defense that participate in the detection and response to pathogens. This frequently results...
BACKGROUND
Platelets are now recognized as immunological sentries in the first line of defense that participate in the detection and response to pathogens. This frequently results in a decrease in the number of circulating platelets. Different mechanisms have been hypothesized to explain the thrombocytopenia in patients with severe dengue, one of them is the participation of the non-structural protein 1 (NS1) of dengue virus (DENV), which can be secreted into circulation during DENV infection and promotes a more efficient infection.
OBJECTIVE
The present study aimed to investigate the ability of platelet response to stimulation with full-length DENV NS1 protein and its domains.
METHODS
DENV NS1 plasmid was transfected into HEK-293T. Proteins were purified by Niquel Sepharose affinity chromatography. Secreted proteins were assessed by sodium dodecylsulfate polyacrylamide gel electrophoresis, Coomassie staining and western blot. Platelet-rich plasma was directly incubated with DENV NS1 proteins. Platelet activation was confirmed by expression of αIIbβIII and P-selectin by flow cytometry. Platelet aggregation was also assessed using DENV NS1 protein and its individual domains as agonists.
RESULTS
DENV NS1 protein and its domains induce P-selectin and αIIbβ3 complex expression on platelet surfaces. DENV NS1 induce a stable platelet aggregation after the addition of a minimal dose of adenosine diphosphate (ADP), epinephrine (EPI), or collagen. Interestingly, only EPI could induce the formation of platelet aggregates after incubation with the protein domains of NS1.
CONCLUSION
Our results suggest that the full DENV NS1 protein and also its domains promote platelet recognition, activation, and aggregation.
Topics: Blood Platelets; Dengue; Dengue Virus; Humans; Platelet Aggregation; Viral Nonstructural Proteins
PubMed: 34160117
DOI: 10.1111/jth.15431 -
Cells Jul 2023Platelets are cellular elements that are physiologically involved in hemostasis, inflammation, thrombotic events, and various human diseases. There is a link between the... (Review)
Review
Platelets are cellular elements that are physiologically involved in hemostasis, inflammation, thrombotic events, and various human diseases. There is a link between the activation of platelets and their metabolism. Platelets possess considerable metabolic versatility. Although the role of platelets in hemostasis and inflammation is known, our current understanding of platelet metabolism in terms of substrate preference is limited. Platelet activation triggers an oxidative metabolism increase to sustain energy requirements better than aerobic glycolysis alone. In addition, platelets possess extra-mitochondrial oxidative phosphorylation, which could be one of the sources of chemical energy required for platelet activation. This review aims to provide an overview of flexible platelet metabolism, focusing on the role of metabolic compartmentalization in substrate preference, since the metabolic flexibility of stimulated platelets could depend on subcellular localization and functional timing. Thus, developing a detailed understanding of the link between platelet activation and metabolic changes is crucial for improving human health.
Topics: Humans; Blood Platelets; Glycolysis; Platelet Activation; Energy Metabolism; Inflammation
PubMed: 37443836
DOI: 10.3390/cells12131802 -
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 -
Annales de Biologie Clinique Feb 2021During primary hemostasis the platelets aggregate to form the platelet thrombus. ADP and thrombin generated by coagulation are the main agonists in platelet aggregation....
During primary hemostasis the platelets aggregate to form the platelet thrombus. ADP and thrombin generated by coagulation are the main agonists in platelet aggregation. In a previous study we were able to show that patients with lung cancer had hypercoagulability, hyperfibrinogemia (≥ 6.22 g/L) was predictive of thromboembolic disease at the start of diagnosis before any therapy. In this study, we studied platelet aggregation in these patients in order to demonstrate whether they have hyperaggregability associated with the hypercoagulability demonstrated previously, and this by evaluating abnormalities in primary hemostasis (platelet count and platelet aggregation). One hundred and one patients diagnosed before any therapy and 72 blood donors were included. Agonists used for platelet aggregation are collagen and adenosine diphosphate at low concentrations. Hyperaggregability is observed when blood platelets are stimulated by ADP at different concentrations (p ≤ 0.01). This hyperaggregability is influenced by the histological type and not the development of the cancer, the age of the subjects and the platelet count, it is independent of hyperfibrinogemia and the occurrence of thromboembolic disease. However, an increase in the platelet level is found in patients with hyperfibrinogemia. Patients with lung cancer present platelet activation observed by aggregometry in response to ADP; which is not influenced by hyperfibrinogemia during cancer.
Topics: Adenosine Diphosphate; Blood Platelets; Humans; Lung Neoplasms; Platelet Aggregation; Thrombin
PubMed: 33648917
DOI: 10.1684/abc.2021.1623