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Aging May 2018The cardiovascular effects of testosterone and dihydrotestosterone are generally attributed to their modulatory action on lipid and glucose metabolism. However, no...
The cardiovascular effects of testosterone and dihydrotestosterone are generally attributed to their modulatory action on lipid and glucose metabolism. However, no studies suggest that circulating androgen levels influence the activation and reactivity of blood platelets - one of the main components of the haemostasis system directly involved in atherosclerosis. The levels of testosterone, dihydrotestosterone and oestradiol in plasma from men and women aged from 60 to 65 years were measured by LC-MS; the aim was to identify any potential relationships between sex steroid levels and the markers of platelet activation (surface membrane expression of GPII/IIIa complex and P-selectin) and platelet reactivity in response to arachidonate, collagen or ADP, monitored with whole blood aggregometry and flow cytometry. The results of the part of the study indicate that the concentrations of testosterone and its reduced form, dihydrotestosterone are significantly negatively associated with platelet activation and reactivity. These observations were confirmed in an model: testosterone and dihydrotestosterone significantly inhibited platelet aggregation triggered by arachidonate or collagen. Our findings indicate that testosterone and dihydrotestosterone are significant haemostatic steroids with inhibitory action on blood platelets in older people.
Topics: Aged; Blood Platelets; Dihydrotestosterone; Estradiol; Female; Humans; Male; Middle Aged; Platelet Activation; Platelet Aggregation; Testosterone
PubMed: 29723157
DOI: 10.18632/aging.101438 -
Molecules (Basel, Switzerland) Dec 2020Coffee is rich in caffeine (CF), chlorogenic acid (CGA) and phenolics. Differing types of coffee beverages and brewing procedures may result in differences in total...
Coffee is rich in caffeine (CF), chlorogenic acid (CGA) and phenolics. Differing types of coffee beverages and brewing procedures may result in differences in total phenolic contents (TPC) and biological activities. Inflammation and increases of platelet activation and aggregation can lead to thrombosis. We focused on determining the chemical composition, antioxidant activity and inhibitory effects on agonist-induced platelet aggregation and cyclooxygenase (COX) of coffee beverages in relation to their preparation method. We prepared instant coffee and brewed coffee beverages using drip, espresso, and boiling techniques. Coffee extracts were assayed for their CF and CGA contents using HPLC, TPC using colorimetry, platelet aggregation with an aggregometer, and COX activity using ELISA. The findings have shown all coffee extracts, except the decaffeinated types, contained nearly equal amounts of CF, CGA, and TPC. Inhibitory effects of coffee extracts on platelet aggregation differed depending on the activation pathways induced by different agonists. All espresso, drip and boiled coffee extracts caused dose dependent inhibition of platelet aggregation induced by ADP, collagen, epinephrine, and arachidonic acid (ARA). The most marked inhibition was seen at low doses of collagen or ARA. Espresso and drip extracts inhibited collagen-induced platelet aggregation more than purified caffeine or CGA. Espresso, boiled and drip coffee extracts were also a more potent inhibitors of COX-1 and COX-2 than purified caffeine or CGA. We conclude that inhibition of platelet aggregation and COX-1 and COX-2 may contribute to anti-platelet and anti-inflammatory effects of espresso and drip coffee extracts.
Topics: Chlorogenic Acid; Chromatography, High Pressure Liquid; Coffea; Coffee; Cyclooxygenase Inhibitors; Molecular Structure; Plant Extracts; Platelet Aggregation; Platelet Aggregation Inhibitors
PubMed: 33375091
DOI: 10.3390/molecules26010010 -
Pannexin-1 Activation by Phosphorylation Is Crucial for Platelet Aggregation and Thrombus Formation.International Journal of Molecular... May 2022Pannexin-1 (PANX1) is a transmembrane protein that forms ion channels as hexamers on the plasma membrane. Electrophysiological studies prove that PANX1 has a high...
Pannexin-1 (PANX1) is a transmembrane protein that forms ion channels as hexamers on the plasma membrane. Electrophysiological studies prove that PANX1 has a high conductance for adenosine triphosphate (ATP), which plays an important role as a signal molecule in platelet activation. Recently, it was shown that PANX1 channels modulate platelet functions. To date, it remains unclear how PANX1 channels are activated and which signaling mechanisms are responsible for impaired hemostasis and thrombosis. Analysis of PANX1 phosphorylation at Tyr and Tyr, and the impact on platelet activation and thrombus formation using genetically modified platelets or pharmacological inhibitors. Platelet activation via immunoreceptor tyrosine-based activation motif (ITAM) coupled, G Protein-Coupled Receptors (GPCR) and thromboxane receptor (TP)-mediated signaling pathways led to increased PANX1 phosphorylation at Tyr and Tyr. We identified the Src-GPVI signaling axes as the main pathway inducing PANX1 activation, while PKC and Akt play a minor role. PANX1 channels function as ATP release channels in platelets to support arterial thrombus formation. PANX1 activation is regulated by phosphorylation at Tyr and Tyr following platelet activation. These results suggest an important role of PANX1 in hemostasis and thrombosis by releasing extracellular ATP to support thrombus formation.
Topics: Adenosine Triphosphate; Animals; Blood Platelets; Connexins; Humans; Mice; Nerve Tissue Proteins; Phosphorylation; Platelet Activation; Platelet Aggregation; Thrombosis
PubMed: 35563450
DOI: 10.3390/ijms23095059 -
Journal of the American Association For... Mar 2022Nonterminal blood sampling in laboratory mice is a very common procedure. With the goal of improving animal welfare, different sampling sites and methods have been...
Nonterminal blood sampling in laboratory mice is a very common procedure. With the goal of improving animal welfare, different sampling sites and methods have been compared but have not achieved a consensus. Moreover, most of these studies overlooked the quality of blood specimens collected. The main preanalytical concern with EDTA-treated blood specimens for hematology analyses is platelet aggregation, which is known to cause analytical errors. Our objective was to find a nonterminal blood sampling method with minimal adverse effects on mice and few or no platelet aggregates. We tested and compared 2 collection sites, 4 sampling methods, and 3 antithrombotic drugs in 80 C57BL6/j male and female mice by evaluating platelet aggregates on blood smears and platelet, WBC, and RBC counts. In addition, the blood collection process was carefully evaluated, and adverse effects were recorded. Platelet aggregation was lower in specimens collected from the jugular vein than from the facial vein, with no effect of the sampling device or the presence of an antithrombotic additive. Highly aggregated specimens were significantly associated with lower platelet counts, whereas aggregation had no effect on WBC or RBC counts. Adverse events during sampling were significantly associated with more numerous platelet aggregates. The jugular vein is thus a satisfactory sampling site in mice in terms of both animal welfare and low platelet aggregation. Using antithrombotic agents appears to be unnecessary, whereas improving sampling conditions remains a key requirement to ensure the quality of EDTA-treated blood specimens from mice.
Topics: Animals; Blood Platelets; Edetic Acid; Female; Male; Mice; Mice, Inbred C57BL; Platelet Aggregation; Platelet Count
PubMed: 35022109
DOI: 10.30802/AALAS-JAALAS-21-000093 -
Molecules (Basel, Switzerland) Feb 2022Flavonoids are compounds with a benzopyranic structure that exhibits multiple pharmacological activities. They are known for their venotonic activity, but their...
Flavonoids are compounds with a benzopyranic structure that exhibits multiple pharmacological activities. They are known for their venotonic activity, but their mechanism of action remains unclear. It is thought that, as this mechanism is mediated by prostaglandins, these compounds may interfere with the arachidonic acid (AA) cascade. These assays are designed to measure the antiplatelet aggregation capacity of quercetin, rutin, diosmetin, diosmin, and hidrosmin, as well as to evaluate a potential structure-activity ratio. In this paper, several studies on platelet aggregation at different concentrations (from 0.33 mM to 1.5 mM) of different flavone compounds are conducted, measuring platelet aggregation by impedance aggregometry, and the cyclooxygenase (COX) activity by metabolites generated, including the activity of the pure recombinant enzyme in the presence of these polyphenols. The results obtained showed that quercetin and diosmetin aglycones have a greater antiplatelet effect and inhibit the COX enzyme activity to a greater extent than their heterosides; however, the fact that greater inhibition of the pure recombinant enzyme was achieved by heterosides suggests that these compounds may have difficulty in crossing biological membranes. In any case, in view of the results obtained, it can be concluded that flavonoids could be useful as coadjuvants in the treatment of cardiovascular pathologies.
Topics: Adult; Blood Platelets; Cyclooxygenase 1; Cyclooxygenase Inhibitors; Female; Flavonoids; Humans; Male; Platelet Aggregation; Platelet Aggregation Inhibitors; Young Adult
PubMed: 35164411
DOI: 10.3390/molecules27031146 -
Nitric Oxide : Biology and Chemistry Feb 2021Nitric oxide, NO, has been explored as a therapeutic agent to treat thrombosis. In particular, NO has potential in treating mechanical device-associated thrombosis due...
Nitric oxide, NO, has been explored as a therapeutic agent to treat thrombosis. In particular, NO has potential in treating mechanical device-associated thrombosis due to its ability to reduce platelet activation and due to the central role of platelet activation and adhesion in device thrombosis. Nitrite is a unique NO donor that reduces platelet activation in that it's activity requires the presence of red blood cells whereas NO activity of other NO donors is blunted by red blood cells. Interestingly, we have previously shown that red blood cell mediated inhibition of platelet activation by adenosine diphosophate (ADP) is dramatically enhanced by illumination with far-red light that is likely due to photolysis of red cell surface bound NO congeners. We now report the effects of nitrite, far-red light, and their combination on several measure of blood coagulation using a variety of agonists. We employed turbidity assays in platelet rich plasma, platelet activation using flow cytometry analysis of a fluorescently labeled antibody to the activated platelet fibrinogen binding site, multiplate impedance-based platelet aggregometry, and assessment of platelet adhesion to collagen coated flow-through microslides. In all cases, the combination of far-red light and nitrite treatment decreased measures of coagulation, but in some cases mono-treatment with nitrite or light alone had no effect. Perhaps most relevant to device thrombosis, we observed that platelet adhesions was inhibited by the combination of nitrite and light treatment while nitrite alone and far-red light alone trended to decrease adhesion, but the results were mixed. These results support the potential of combined far-red light and nitrite treatment for preventing thrombosis in extra-corporeal or shallow-tissue depth devices where the far-red light can penetrate. Such a combined treatment could be advantageous due to the localized treatment afforded by far-red light illumination with minimal systemic effects. Given the role of thrombosis in COVID 19, application to treatment of patients infected with SARS Cov-2 might also be considered.
Topics: Blood Coagulation; Blood Platelets; COVID-19; Humans; Light; Nitric Oxide; Nitric Oxide Donors; Nitrites; Platelet Activation; Platelet Adhesiveness; Platelet Aggregation; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 33271226
DOI: 10.1016/j.niox.2020.11.005 -
Iranian Journal of Medical Sciences Nov 2022Platelet aggregation is a crucial mechanism in the progression of atherothrombotic events. This systematic review aims to introduce the plants studied in healthy people... (Review)
Review
BACKGROUND
Platelet aggregation is a crucial mechanism in the progression of atherothrombotic events. This systematic review aims to introduce the plants studied in healthy people as the primary prevention to inhibit platelet aggregation. We also discuss possible mechanisms that are involved in the inhibition of platelet aggregation.
METHODS
A systematic search on the electronic medical databases from 1970 to February 2020 was performed. The selected keywords were: "herb", "plant", "platelet aggregation", "platelet activation", "clinical trial", "randomized" and "controlled".
RESULTS
The result of the initial search was a pool of 136 articles. After initial abstract reviewing, there were 55 relevant articles. Finally, 28 eligible records fulfilled our inclusion criteria to enter the qualitative synthesis process.
CONCLUSION
Out of the 10 plants evaluated in the clinical trials, nine had inhibitory effects on platelet aggregation. Most of the reviewed plants, including tomato ( L), garlic (), kiwifruit (), cacao (), grape (), ginkgo (), flaxseed (), sea buckthorn berry (), and argan () could be potential sources for the primary prevention of atherothrombotic events at an appropriate dosage. Finally, we do not consider phytoceuticals as a replacement for the guideline-directed medical treatment. Large randomized double-blind clinical trials are required to evaluate the anti-platelet characteristics of these plants for the adjuvant primary prevention of cardiovascular disease.
Topics: Humans; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Platelet Aggregation; Ginkgo biloba; Garlic; Hippophae; Primary Prevention
PubMed: 36380973
DOI: 10.30476/IJMS.2021.91328.2247 -
Journal of Thrombosis and Thrombolysis May 2018The stability of an arterial thrombus, determined by its structure and ability to resist endogenous fibrinolysis, is a major determinant of the extent of infarction that... (Review)
Review
The stability of an arterial thrombus, determined by its structure and ability to resist endogenous fibrinolysis, is a major determinant of the extent of infarction that results from coronary or cerebrovascular thrombosis. There is ample evidence from both laboratory and clinical studies to suggest that in addition to inhibiting platelet aggregation, antithrombotic medications have shear-dependent effects, potentiating thrombus fragility and/or enhancing endogenous fibrinolysis. Such shear-dependent effects, potentiating the fragility of the growing thrombus and/or enhancing endogenous thrombolytic activity, likely contribute to the clinical effectiveness of such medications. It is not clear how much these effects relate to the measured inhibition of platelet aggregation in response to specific agonists. These effects are observable only with techniques that subject the growing thrombus to arterial flow and shear conditions. The effects of antithrombotic medications on thrombus stability and ways of assessing this are reviewed herein, and it is proposed that thrombus stability could become a new target for pharmacological intervention.
Topics: Fibrinolysis; Fibrinolytic Agents; Humans; Platelet Aggregation; Thrombosis
PubMed: 29550950
DOI: 10.1007/s11239-018-1641-2 -
Nutrients Jun 2020Platelet hyper-activation and platelet microparticles (PMPs) play a key role in the pathogenesis of cardiovascular diseases. Dietary polyphenols are believed to mimic...
Platelet hyper-activation and platelet microparticles (PMPs) play a key role in the pathogenesis of cardiovascular diseases. Dietary polyphenols are believed to mimic antiplatelet agents by blunting platelet activation receptors via its antioxidant phenomenon. However, there is limited information on the anti-platelet activity of grain-derived polyphenols. The aim of the study is to evaluate the effects of sorghum extract (Shawaya short black 1 variety), an extract previously characterised for its high antioxidant activity and reduction of oxidative stress-related endothelial dysfunction, on platelet aggregation, platelet activation and PMP release. Whole blood samples collected from 18 healthy volunteers were treated with varying non-cytotoxic concentrations of polyphenol-rich black sorghum extract (BSE). Platelet aggregation study utilised 5 µg/mL collagen to target the GPVI pathway of thrombus formation whereas adenine phosphate (ADP) was used to stimulate the P2Y1/P2Y12 pathway of platelet activation assessed by flow cytometry. Procaspase-activating compound 1 (PAC-1) and P-selectin/CD62P were used to evaluate platelet activation- related conformational changes and degranulation respectively. PMPs were isolated from unstimulated platelets and quantified by size distribution and binding to CD42b. BSE treatment significantly reduced both collagen-induced platelet aggregation and circulatory PMP release at 40 µg/mL ( 0.001) when compared to control. However, there was no significant impact of BSE on ADP-induced activation-dependent conformational change and degranulation of platelets. Results of this study suggest that phenolic rich BSE may confer cardio-protection by modulating specific signalling pathways involved in platelet activation and PMP release.
Topics: Antioxidants; Blood Platelets; Cell-Derived Microparticles; Flow Cytometry; Humans; Oxidative Stress; Plant Extracts; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Polyphenols; Sorghum
PubMed: 32545505
DOI: 10.3390/nu12061760 -
Blood Apr 2017
Topics: Blood Platelets; Lectins, C-Type; Platelet Aggregation
PubMed: 28385772
DOI: 10.1182/blood-2017-02-764670