-
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 -
Bioconjugate Chemistry Jul 2022. Platelets are small, mechanosensitive blood cells responsible for maintaining vascular integrity and activatable on demand to limit bleeding and facilitate thrombosis....
. Platelets are small, mechanosensitive blood cells responsible for maintaining vascular integrity and activatable on demand to limit bleeding and facilitate thrombosis. While circulating in the blood, platelets are exposed to a range of mechanical and chemical stimuli, with the platelet membrane being the primary interface and transducer of outside-in signaling. Sensing and modulating these interface signals would be useful to study mechanochemical interactions; yet, to date, no methods have been defined to attach adducts for sensor fabrication to platelets without triggering platelet activation. We hypothesized that DNA origami, and methods for its attachment, could be optimized to enable nonactivating instrumentation of the platelet membrane. . We designed and fabricated multivalent DNA origami nanotile constructs to investigate nanotile hybridization to membrane-embedded single-stranded DNA-tetraethylene glycol cholesteryl linkers. Two hybridization protocols were developed and validated (Methods I and II) for rendering high-density binding of DNA origami nanotiles to human platelets. Using quantitative flow cytometry, we showed that DNA origami binding efficacy was significantly improved when the number of binding overhangs was increased from two to six. However, no additional binding benefit was observed when increasing the number of nanotile overhangs further to 12. Using flow cytometry and transmission electron microscopy, we verified that hybridization with DNA origami constructs did not cause alterations in the platelet morphology, activation, aggregation, or generation of platelet-derived microparticles. . Herein, we demonstrate that platelets can be successfully instrumented with DNA origami constructs with no or minimal effect on the platelet morphology and function. Our protocol allows for efficient high-density binding of DNA origami to platelets using low quantities of the DNA material to label a large number of platelets in a timely manner. Nonactivating platelet-nanotile adducts afford a path for advancing the development of DNA origami nanoconstructs for cell-adherent mechanosensing and therapeutic agent delivery.
Topics: Blood Platelets; Cell-Derived Microparticles; DNA; DNA Adducts; Humans; Platelet Activation
PubMed: 35731951
DOI: 10.1021/acs.bioconjchem.2c00197 -
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 -
Dermatology (Basel, Switzerland) 2021Psoriasis is an immune-mediated inflammatory skin disease in conjunction with the systemic inflammatory process. It appears to be related to increased risks of... (Review)
Review
BACKGROUND
Psoriasis is an immune-mediated inflammatory skin disease in conjunction with the systemic inflammatory process. It appears to be related to increased risks of cardiovascular disease events, especially in severe cases. The hemostatic balance is disrupted due to the prothrombotic bias in psoriasis, which might be mainly preserved by platelet hyperactivity. Platelets are also immune cells that initiate and regulate immune and inflammatory processes, except as the principal mediator of hemostasis and thrombosis, and platelet dysfunction is deeply involved in the pathogenesis of psoriasis.
SUMMARY
The aim of this study is to perform a review that expounds abnormal platelet function in psoriasis and explains the important role of platelets in the pathogenic mechanism of psoriasis in order to provide new targets for comprehensive medical treatment.
Topics: Blood Platelets; Humans; Platelet Activation; Psoriasis
PubMed: 32349003
DOI: 10.1159/000505536 -
Prostaglandins & Other Lipid Mediators Dec 2023Platelets are one of the key mediators in thrombosis as well as in the progression of many diseases. An increase in platelet activation and a decrease in platelet count... (Review)
Review
Platelets are one of the key mediators in thrombosis as well as in the progression of many diseases. An increase in platelet activation and a decrease in platelet count is associated with a plethora of liver diseases. In non-alcoholic fatty liver disease (NAFLD), platelets are highly activated and participate in the disease progression by enhancing the pro-thrombotic and pro-inflammatory state. Some altered platelet parameters such as mean platelet volume, plateletcrits, and platelet distribution width, aspartate transaminase to platelet ratio index, liver stiffness to platelet ratio and red cell distribution width to platelet ratio were found to be associated with NAFLD disease. Further, platelet contributes to the progression of cardiovascular complications in NAFLD is gaining the researcher's attention. An elevated mean platelet volume is known to enhance the risk of stroke, atherosclerosis, thrombosis, and myocardial infarction in NAFLD. Evidence also suggested that modulation in platelet function using aspirin, ticlopidine, and cilostazol help in controlling the NAFLD progression. Future research should focus on antiplatelet therapy as a treatment strategy that can control platelet activation in NAFLD as well as its cardiovascular risk. In the present review, we have detailed the role of platelets in NAFLD and its cardiovascular complications. We further aimed to highlight the growing need for antiplatelet therapy in NAFLD.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Platelet Aggregation Inhibitors; Blood Platelets; Platelet Activation; Thrombosis; Liver
PubMed: 37479133
DOI: 10.1016/j.prostaglandins.2023.106766 -
Cell Reports Methods Jul 2023A characteristic clinical complication in cancer patients is the frequent incidence of thrombotic events. Numerous studies have shown hyperactive/activated platelets to...
A characteristic clinical complication in cancer patients is the frequent incidence of thrombotic events. Numerous studies have shown hyperactive/activated platelets to be a critical earlier trigger for cancer-associated thrombus formation. However, there currently is no viable approach to monitor specific changes in tumor-associated platelet activity. Here, we describe a chromatograph-like microfluidic device that is highly sensitive to the activity status of peripheral circulating platelets in both tumor-bearing mice and clinical cancer patients. Our results show a strongly positive correlation between platelet activation status and tumor progression. Six-month follow-up data from advanced cancer patients reveal positive links between platelet activity level and thrombus occurrence rate, with a high predictive capacity of thrombotic events (AUC = 0.842). Our findings suggest that circulating platelet activity status determined by this microfluidic device exhibits sensitive, predictive potential for thrombotic events in cancer patients for directing well-timed antithrombosis treatment.
Topics: Mice; Animals; Blood Platelets; Platelet Activation; Thrombosis; Neoplasms
PubMed: 37533637
DOI: 10.1016/j.crmeth.2023.100513 -
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 -
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 -
Platelets 2020
Topics: Blood Coagulation; Blood Platelets; Female; Humans; Platelet Activation; Platelet Function Tests; Pre-Eclampsia; Pregnancy
PubMed: 31340711
DOI: 10.1080/09537104.2019.1646901 -
Seminars in Thrombosis and Hemostasis Mar 2024CD36 (also known as platelet glycoprotein IV) is expressed by a variety of different cell entities, where it possesses functions as a signaling receptor, but... (Review)
Review
CD36 (also known as platelet glycoprotein IV) is expressed by a variety of different cell entities, where it possesses functions as a signaling receptor, but additionally acts as a transporter for long-chain fatty acids. This dual function of CD36 has been investigated for its relevance in immune and nonimmune cells. Although CD36 was first identified on platelets, the understanding of the role of CD36 in platelet biology remained scarce for decades. In the past few years, several discoveries have shed a new light on the CD36 signaling activity in platelets. Notably, CD36 has been recognized as a sensor for oxidized low-density lipoproteins in the circulation that mitigates the threshold for platelet activation under conditions of dyslipidemia. Thus, platelet CD36 transduces atherogenic lipid stress into an increased risk for thrombosis, myocardial infarction, and stroke. The underlying pathways that are affected by CD36 are the inhibition of cyclic nucleotide signaling pathways and simultaneously the induction of activatory signaling events. Furthermore, thrombospondin-1 secreted by activated platelets binds to CD36 and furthers paracrine platelet activation. CD36 also serves as a binding hub for different coagulation factors and, thus, contributes to the plasmatic coagulation cascade. This review provides a comprehensive overview of the recent findings on platelet CD36 and presents CD36 as a relevant target for the prevention of thrombotic events for dyslipidemic individuals with an elevated risk for thrombosis.
Topics: Humans; CD36 Antigens; Blood Platelets; Platelet Activation; Thrombosis; Biology
PubMed: 37192651
DOI: 10.1055/s-0043-1768935