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Current Medicinal Chemistry 2016Nanomaterials can get into the blood circulation after injection or by release from implants but also by permeation of the epithelium after oral, respiratory or dermal... (Review)
Review
Nanomaterials can get into the blood circulation after injection or by release from implants but also by permeation of the epithelium after oral, respiratory or dermal exposure. Once in the blood, they can affect hemostasis, which is usually not intended. This review addresses effects of biological particles and engineered nanomaterials on hemostasis. The role of platelets and coagulation in normal clotting and the interaction with the immune system are described. Methods to identify effects of nanomaterials on clotting and results from in vitro and in vivo studies are summarized and the role of particle size and surface properties discussed. The literature overview showed that mainly pro-coagulative effects of nanomaterials have been described. In vitro studies suggested stronger effects of smaller than of larger NPs on coagulation and a greater importance of material than of surface charge. For instance, carbon nanotubes, polystyrene particles, and dendrimers inferred with clotting independent from their surface charge. Coating of particles with polyethylene glycol was able to prevent interaction with clotting by some particles, while it had no effect on others and the more recently developed bio-inspired surfaces might help to design coatings for more biocompatible particles. The mainly pro-coagulative action of nanoparticles could present a particular risk for individuals affected by common diseases such as diabetes, cancer, and cardiovascular diseases. Under standardized conditions, in vitro assays using human blood appear to be a suitable tool to study mechanisms of interference with hemostasis and to optimize hemocompatibility of nanomaterials.
Topics: Biocompatible Materials; Blood Coagulation; Hemostasis; Humans; Nanoparticles; Platelet Activation
PubMed: 26063498
DOI: 10.2174/0929867323666160106151428 -
High Blood Pressure & Cardiovascular... Sep 2015Many drugs are nowadays available to inhibit platelet activation and aggregation, especially in patients with acute coronary syndromes and undergoing percutaneous... (Review)
Review
Many drugs are nowadays available to inhibit platelet activation and aggregation, especially in patients with acute coronary syndromes and undergoing percutaneous coronary intervention with stent implantation. Primary targets are represented by enzymes or receptors involved in platelet activation. Genetic mutations in these targets contribute to the inter-individual variability in platelet responses therefore weakening the efficacy of antiplatelet agents. High on treatment platelet reactivity is a condition characterized by low levels of platelet inhibition despite the use of antiplatelet drugs. This could be responsible for re-infarction, stent-thrombosis and strokes, affecting short and long-term prognosis after coronary revascularization. So far, to test antiplatelet resistance either the assessment of platelet function or the identification of genetic carriers of poly morphisms have been pursued. Although several methods are now available to test platelet reactivity, it is still debated whether its routine assessment gives real benefits in clinical practice. The present review aims at examining current evidences on genetic polymorphisms affecting optimal platelet inhibition.
Topics: Blood Platelets; Clopidogrel; Cytochrome P-450 CYP2C19; Drug Resistance; Humans; Membrane Glycoproteins; Mutation; Platelet Activation; Platelet Adhesiveness; Platelet Aggregation; Platelet Aggregation Inhibitors; Polymorphism, Genetic; Receptors, Adrenergic, alpha; Receptors, Adrenergic, beta; Ticlopidine
PubMed: 25986078
DOI: 10.1007/s40292-015-0104-5 -
International Journal of Cardiology Nov 2023
Topics: Humans; Platelet Activation; Syndrome; Takotsubo Cardiomyopathy
PubMed: 37586422
DOI: 10.1016/j.ijcard.2023.131256 -
Current Drug Targets 2015Platelets play a crucial role in immune responses. Impaired platelet activation may cause persistent mucosal inflammation through P-selectin, CD40-CD40L and other... (Review)
Review
Platelets play a crucial role in immune responses. Impaired platelet activation may cause persistent mucosal inflammation through P-selectin, CD40-CD40L and other systems influencing granulocytes, macrophages or endothelial cells. Pharmacological regulation of platelet activation may reduce thromboembolism and limit the interaction of platelets with endothelial and inflammatory cells, in turn weakening the inflammatory responses. In this review we focus on pathophysiological activities of platelets in inflammatory bowel diseases and discuss the studies on currently available anti-platelet therapies in the treatment of gastrointestinal inflammation. Finally, we provide a prospective view to new anti-platelet agents currently under development.
Topics: Animals; Blood Platelets; Humans; Inflammatory Bowel Diseases; Platelet Activation; Platelet Aggregation Inhibitors
PubMed: 25585124
DOI: 10.2174/1389450116666150113122229 -
International Journal of Molecular... Apr 2024Thrombosis is the pathological clot formation under abnormal hemodynamic conditions, which can result in vascular obstruction, causing ischemic strokes and myocardial... (Review)
Review
Thrombosis is the pathological clot formation under abnormal hemodynamic conditions, which can result in vascular obstruction, causing ischemic strokes and myocardial infarction. Thrombus growth under moderate to low shear (<1000 s) relies on platelet activation and coagulation. Thrombosis at elevated high shear rates (>10,000 s) is predominantly driven by unactivated platelet binding and aggregating mediated by von Willebrand factor (VWF), while platelet activation and coagulation are secondary in supporting and reinforcing the thrombus. Given the molecular and cellular level information it can access, multiscale computational modeling informed by biology can provide new pathophysiological mechanisms that are otherwise not accessible experimentally, holding promise for novel first-principle-based therapeutics. In this review, we summarize the key aspects of platelet biorheology and mechanobiology, focusing on the molecular and cellular scale events and how they build up to thrombosis through platelet adhesion and aggregation in the presence or absence of platelet activation. In particular, we highlight recent advancements in multiscale modeling of platelet biorheology and mechanobiology and how they can lead to the better prediction and quantification of thrombus formation, exemplifying the exciting paradigm of digital medicine.
Topics: Humans; Thrombosis; Blood Platelets; Hemostasis; Platelet Activation; Animals; Platelet Adhesiveness; Platelet Aggregation
PubMed: 38732019
DOI: 10.3390/ijms25094800 -
International Journal of Molecular... Nov 2021Cardiovascular disease is strongly influenced by platelet activation. Platelet activation and thrombus formation at atherosclerotic plaque rupture sites is a dynamic... (Review)
Review
Cardiovascular disease is strongly influenced by platelet activation. Platelet activation and thrombus formation at atherosclerotic plaque rupture sites is a dynamic process regulated by different signaling networks. Therefore, there are now focused efforts to search for novel bioactive compounds which target receptors and pathways in the platelet activation process while preserving normal hemostatic function. The antiplatelet activity of numerous fruits and vegetables and their multiple mechanisms of action have recently been highlighted. In this review, we review the antiplatelet actions of bioactive compounds via key pathways (protein disulfide isomerase, mitogen-activated protein kinases, mitochondrial function, cyclic adenosine monophosphate, Akt, and shear stress-induced platelet aggregation) with no effects on bleeding time. Therefore, targeting these pathways might lead to the development of effective antiplatelet strategies that do not increase the risk of bleeding.
Topics: Animals; Blood Platelets; Hemorrhage; Hemostasis; Humans; Phytochemicals; Plaque, Atherosclerotic; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; Thrombosis
PubMed: 34830261
DOI: 10.3390/ijms222212380 -
Platelets 2019Platelets and Toll-like receptor (TLR) signalling play a role in the immune response during sepsis. Although preclinical knowledge about the role of platelet TLR...
Platelets and Toll-like receptor (TLR) signalling play a role in the immune response during sepsis. Although preclinical knowledge about the role of platelet TLR signalling is increasing, data during human sepsis are less abundant. Moreover, controversy remains about the effect of the TLR4 agonist lipopolysaccharide (LPS) on platelet activation. We therefore assessed platelet TLR expression during human and murine sepsis. Moreover, we investigated the effect of TLR4 signalling on platelet activation and TLR expression. Platelets from healthy controls stimulated with LPS did not show classical platelet activation (P-selectin, CD63 and phosphatidylserine expression), potentiation of subthreshold agonist stimulation nor platelet-leukocyte complex formation. LPS stimulation however did increase maximal mitochondrial respiration in a TLR4-dependent manner. Platelet stimulation with LPS did not alter TLR expression. Platelet stimulation with thrombin receptor activating peptide increased TLR5 and TLR9, but not TLR2 or TLR4 expression. Platelets from patients with sepsis and mice with experimental sepsis showed platelet activation, but unaltered TLR expression. These results indicate that sepsis-induced platelet activation is not associated with altered platelet TLR expression and, although platelets are responsive to LPS, stimulation of platelet TLR4 does not result in classical platelet activation.
Topics: Animals; Blood Platelets; Female; Humans; Lipopolysaccharides; Mice; Platelet Activation; Sepsis; Signal Transduction; Toll-Like Receptors
PubMed: 29528268
DOI: 10.1080/09537104.2018.1445841 -
Middle East African Journal of... 2021The aim of the present study was to assess platelet activation by analyzing three platelet activation parameters in ocular Behçet's disease (BD): mean platelet volume...
PURPOSE
The aim of the present study was to assess platelet activation by analyzing three platelet activation parameters in ocular Behçet's disease (BD): mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT).
METHODS
Twenty-nine patients with active ocular BD (Group 1), 40 patients with inactive ocular BD (Group 2), and 40 healthy adult individuals serving as controls (Group 3) were evaluated. All of the individuals had been performed the complete ophthalmologic evaluation. The levels of MPV, PDW, and PCT were measured in each group.
RESULTS
The mean MPV level was 8.40 ± 0.97 in Group 1, 8.32 ± 1.04 in Group 2, and 7.77 ± 0.72 in Group 3. The mean PDW level was 15.12 ± 1.09 in Group 1, 14.97 ± 1.02 in Group 2, and 14.52 ± 0.82 in Group 3. The mean PCT level was 0.23 ± 0.07 in Group 1, 0.21 ± 0.04 in Group 2, and 0.18 ± 0.03 in Group 3. MPV, PDW, and PCT levels were significantly higher in ocular BD patients than controls ( < 0.05).
CONCLUSION
Platelet activation may affect vascular occlusion in ocular Behçet's patients with posterior segment involvement. This result may be important in evaluating ocular BD patients.
Topics: Adult; Behcet Syndrome; Humans; Mean Platelet Volume; Platelet Activation
PubMed: 35719287
DOI: 10.4103/meajo.MEAJO_324_19 -
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 -
Cellular Physiology and Biochemistry :... 2017The retinoid X receptor (RXRs) stimulator Bexarotene ((4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl] benzoic acid) is used for the treatment of...
BACKGROUND/AIMS
The retinoid X receptor (RXRs) stimulator Bexarotene ((4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl] benzoic acid) is used for the treatment of several malignancies. Bexarotene is at least in part effective by stimulation of apoptosis of tumor cells. Moreover, Bexarotene triggers eryptosis, the suicidal death of erythrocytes. Similar to erythrocytes, blood platelets lack nuclei but are nevertheless able to enter an apoptosis-like phenotype, characterized by caspase activation, cell shrinkage and cell membrane scrambling with phospha-tidylserine translocation to the cell surface. Platelet apoptosis is triggered by increase of cytosolic Ca2+-activity ([Ca2+]i), which further leads to degranulation and integrin activation. Platelet activation and apoptosis could be elicited by thrombin or collagen related peptide (CRP). The present study explored whether treatment of platelets with bexarotene modifies platelet activation and apoptosis following exposure to thrombin or CRP.
METHODS
Platelets isolated from wild-type mice were exposed for 30 minutes to bexarotene (6 µg/ml) without or with an additional treatment with thrombin (0.01 U/ml) or CRP (2 µg/ml or 5 µg/ml). Flow cytometry was employed to estimate cytosolic Ca2+-activity ([Ca2+]i) from Fluo-3 fluorescence, platelet degranulation from P-selectin abundance, integrin activation from αIIbβ3 integrin abundance, caspase activity utilizing an Active Caspase-3 Staining kit, phosphatidylserine abundance from annexin-V-binding, and relative platelet volume from forward scatter.
RESULTS
In the absence of thrombin or CRP, the administration of bexarotene slightly but significantly increased [Ca2+]i, but did not significantly modify P-selectin abundance, activated αIIbβ3 integrin, annexin-V-binding, cell volume, or caspase activity. Exposure of platelets to thrombin or CRP was followed by significant increase of [Ca2+]i, P-selectin abundance, active αIIbβ3 integrin, annexin-V-binding, and caspase activity. The effects of thrombin on [Ca2+]i, annexin-V-binding, cell volume, and caspase activity as well as the effects of CRP on [Ca2+]i, P-selectin abundance, activated αIIbβ3 integrin, annexin-V-binding, cell volume, and caspase activity were significantly augmented in the presence of bexarotene.
CONCLUSIONS
Bexarotene sensitizes blood platelets for thrombin and/or CRP induced activation and apoptosis.
Topics: Animals; Apoptosis; Bexarotene; Blood Platelets; Calcium; Collagen; Erythrocytes; Flow Cytometry; Hemolysis; Humans; Mice; Platelet Activation; Platelet Glycoprotein GPIIb-IIIa Complex; Reactive Oxygen Species; Tetrahydronaphthalenes; Thrombin
PubMed: 28641286
DOI: 10.1159/000478627