The impact of inhibition of multidrug resistance protein 4 (MRP4) on nitric oxide (NO) resistance and on ADP-induced platelet aggregation is unknown. The aim of this investigation was to verify whether platelet NO resistance correlates with MRP4 expression and evaluate whether this can be reduced by in vitro MRP4 inhibition mediated by cilostazol. Moreover, we assessed if inhibition of MRP4-mediated transport reduces ADP-induced platelet reactivity. The inhibitory effect of sodium nitroprusside (SNP), a NO-donor that enhances cyclic guanosine monophosphate (cGMP) cytosolic concentration, was assessed in platelets obtained from aspirin treated patients and in a control population. The inhibitory effect of SNP was evaluated by ADP-induced aggregation in SNP-treated platelets. The impact of MRP4 on ADP-induced platelet aggregation was performed in high on aspirin residual platelet reactivity (HARPR) patients and compared to healthy volunteers (HV), and a control cohort (CTR). In aspirin-treated patients with high levels of MRP4, reduced SNP inhibition was found compared to those with low levels of MRP4. MRP4 inhibition by cilostazol significantly reduced ADP-induced platelet aggregation in HARPR population, and to a lesser extent in HV and CTR populations. In conclusion, cilostazol can mitigate the hyper-reactive platelet phenotype of HARPR patients by reducing residual ADP-induced platelet aggregation and increasing NO-dependent endothelial antiplatelet effects.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049923 | PMC |
| http://dx.doi.org/10.1007/s11239-020-02214-4 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
In vitro and in vivo effects of mesoporous silica nanoparticles (MSN) on the functional activity of platelets were studied in experiments on white rats. MSN particles, neither uncoated nor coated with calcium alginate, induced spontaneous platelet aggregation when added to platelet-rich plasma, but significantly enhanced ADP-induced platelet aggregation. Subcutaneous administration of uncoated and calcium alginate-coated MSN resulted in increased maximum size and rate of platelet aggregate formation 1 day post-injection.
View Article and Find Full Text PDFDistinct Hemostasis and Blood Composition in Spiny Mouse .
Int J Mol Sci
November 2024
Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia.
Article Synopsis
- The spiny mouse exhibits the ability to heal wounds without scarring, which may be linked to unique features of its blood and clotting mechanisms.
- Compared to Balb/c mice, spiny mice showed stronger blood clots, faster tail bleeding times, and higher levels of clottable fibrinogen, indicating superior hemostatic capabilities.
- Histological analysis revealed that spiny mouse clots were densely packed with fibrin and had better plasma clot stiffness, suggesting that these characteristics could enhance their wound healing and regenerative abilities.
Exploring the morphine-platelet activity association in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention.
Platelets
December 2024
Department of Cardiology, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
Article Synopsis
- STEMI is typically triggered by a ruptured plaque, leading to blood clot formation, and treatments like platelet inhibitors and PCI are crucial for recovery.
- This study, part of the VALIDATE-SWEDHEART trial, analyzed 89 STEMI patients to examine how morphine, used for pain relief, affects platelet activity after treatment with ticagrelor and primary PCI.
- Results indicated that morphine treatment was associated with higher platelet aggregation one hour after PCI, but did not impact inflammation biomarkers or show significant differences before or twelve hours post-PCI.
Assay variables and early clinical evaluation of low-angle light scattering for platelet function analysis.
Int J Hematol
December 2024
National Medical Research Center of Pediatric Hematology, Oncology and Immunology Named After Dmitry Rogachev, Russian Ministry of Healthcare, Moscow, Russian Federation.
Introduction: The recently developed platelet aggregation technique based on low-angle light scattering (LaSca) in diluted platelet-rich plasma (PRP) requires only a small sample volume and provides information about platelet aggregation and shape change. This study aimed to investigate the influence of preanalytical and analytical variables and to validate the method in a real-life pediatric hematology hospital setting.
Methods: Platelet aggregation was induced by ADP in diluted PRP in the presence of 2 mM calcium at 23 °C.
Molecular Biomarkers for In Vitro Thrombogenicity Assessment of Medical Device Materials.
J Biomed Mater Res B Appl Biomater
October 2024
Division of Applied Mechanics, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
To develop standardized in vitro thrombogenicity test methods for evaluating medical device materials, three platelet activation biomarkers, beta-thromboglobulin (β-TG), platelet factor 4 (PF4), soluble p-selectin (CD62P), and a plasma coagulation marker, thrombin-antithrombin complex (TAT), were investigated. Whole blood, drawn from six healthy human volunteers into Anticoagulant Citrate Dextrose Solution A was recalcified and heparinized over a concentration range of 0.5-1.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!