MicroRNA as Potential Biomarkers of Platelet Function on Antiplatelet Therapy: A Review.
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ABSTRACT:
SUBMITTER: Czajka P
PROVIDER: S-EPMC8081881 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionPatients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) require dual antiplatelet therapy (DAPT). However, the response to treatment can vary considerably. Certain platelet microRNAs (miRs) are suspected to predict DAPT response and influence platelet function. This study aimed to analyze selected miRs' expressions and compare them among patients treated with different P2Y12 inhibitors while assessing their association with platelet activity and turnover parameters.Materials and methodsWe recruited 79 ACS patients post-PCI treated with clopidogrel, ticagrelor, or prasugrel, along with 18 healthy volunteers. Expression levels of miR-126-3p, miR223-3p, miR-21-5p, miR-197-3p, and miR-24-3p, as well as immature platelet fraction (IPF) and ADP-induced platelet reactivity, were measured and compared between groups.ResultsAnalyses revealed significantly lower expressions of miR-126-3p, miR-223-3p, miR-21-5p, and miR-197-3p in patients treated with ticagrelor, compared to clopidogrel (fold changes from -1.43 to -1.27, p-values from 0.028 to 0.048). Positive correlations were observed between platelet function and the expressions of miR-223-3p (r = 0.400, p = 0.019) and miR-21-5p (r = 0.423, p = 0.013) in patients treated with potent drugs. Additionally, miR-24-3p (r = 0.411, p = 0.012) and miR-197-3p (r = 0.333, p = 0.044) showed correlations with IPF.ConclusionsThe identified platelet miRs hold potential as biomarkers for antiplatelet therapy. (ClinicalTrials.gov number, NCT06177587).
| S-EPMC10780110 | biostudies-literature
Project description:Cardiovascular diseases are the leading cause of death in the Western world. Several factors have led to the increase in vascular disorders, including the aging population, unhealthy lifestyles, increasing rates of diabetes and raised lipids, and further risk factors resulting in inflammation and calcification of the vascular endothelium. Activated platelets in damaged blood vessels can trigger arterial thrombus formation, leading to vascular occlusion with subsequent organ hypoperfusion and clinical manifestation of myocardial infarction, stroke, or peripheral artery disease. Platelet inhibitors such as aspirin and clopidogrel (Plavix(®) and generics) are prescribed as primary or secondary prevention to attenuate chronic platelet activation. However, a significant proportion of patients do not respond adequately to uniform antiplatelet treatment. These 'non-responders' have an increased risk for stent thrombosis, stroke, and other ischemic complications. Platelet function (PF) tests can identify these patients thus enabling physicians to offer personalized and alternative treatment strategies. Recent alternatives to clopidogrel include prasugrel (Efient(®)) and ticagrelor (Brilique(®)) - that are both more potent than clopidogrel but also more expensive and associated with a higher risk of bleeding complications. Given these drawbacks, PF testing might help clinicians to prescribe optimal antiplatelet agent to maximize patient safety and efficacy while minimizing costs. While randomized studies using different test systems have left clinicians puzzled about the medical value of tailored antiplatelet therapy, accumulated evidence from recent studies on tailored antiplatelet therapies and the association with improved outcomes have now resulted in a consensus expert opinion for the specific adoption of PF diagnostics into clinical practice.
| S-EPMC4975182 | biostudies-other
Project description:The purpose of this study was to identify changes in platelet mRNA that result from exposure to antiplatelet therapy. A total of 84 healthy volunteers were recruited into a longitudinal study of various antiplatelet exposures with 58 completing all study visits. This was a 5 visit study where each visit was separated by ~ 4 weeks. At each Visit purified platelets using a CD45 negative selection protocol was performed in addition to platelet function testing using light transmittance aggregometry (ADP, EPI, and Collagen) and PFA100 (Col/EPI). After the baseline visit (V1), participants were randomized to receive 81mg/day or 325mg/day aspirin x 4 weeks followed by Visit 2. Participants then crossed over to the alternative dose of aspirin for 4 weeks followed by Visit 3. Between Visits 3 and 4 participants washed out their aspirin for 4 weeks. The final exposure was ticagrelor 90mg twice daily x 4 weeks until Visit 5.
2022-03-14 | GSE158765 | GEO
Project description:Given the high morbidity and mortality of cardiovascular diseases (CVDs), novel biomarkers for platelet reactivity are urgently needed. Ischemic events in CVDs are causally linked to platelets, small anucleate cells important for hemostasis. The major side-effect of antiplatelet therapy are life-threatening bleeding events. Current platelet function tests are not sufficient in guiding treatment decisions. Platelets host a broad spectrum of microRNAs (miRNAs) and are a major source of cell-free miRNAs in the blood stream. Platelet-related miRNAs have been suggested as biomarkers of platelet activation and assessment of antiplatelet therapy responsiveness. Platelets release miRNAs upon activation, possibly leading to alterations of plasma miRNA levels in conjunction with CVD or inadequate platelet inhibition. Unlike current platelet function tests, which measure platelet activation ex vivo, signatures of platelet-related miRNAs potentially enable the assessment of in vivo platelet reactivity. Evidence suggests that some miRNAs are responsive to platelet inhibition, making them promising biomarker candidates. In this review, we explain the secretion of miRNAs upon platelet activation and discuss the potential use of platelet-related miRNAs as biomarkers for CVD and antiplatelet therapy monitoring, but also highlight remaining gaps in our knowledge and uncertainties regarding clinical utility. We also elaborate on technical issues and limitations concerning plasma miRNA quantification.
| S-EPMC7278969 | biostudies-literature
Project description:BackgroundAspirin and P2Y12 antagonists are antiplatelet compounds that are used clinically in patients with thrombosis. However, some patients are 'resistant' to antiplatelet therapy, which increases their risk of developing acute coronary syndromes. These patients often present with an underlying condition that is associated with altered levels of circulating platelet primers and platelet hyperactivity. Platelet primers cannot stimulate platelet activation, but, in combination with physiologic stimuli, significantly enhance platelet function.ObjectivesTo explore the role of platelet primers in resistance to antiplatelet therapy, and to evaluate whether phosphoinositide 3-kinase (PI3K) contributes to this process.Methods and resultsWe used platelet aggregation, thromboxane A2 production and ex vivo thrombus formation as functional readouts of platelet activity. Platelets were treated with the potent P2Y12 inhibitor AR-C66096, aspirin, or a combination of both, in the presence or absence of the platelet primers insulin-like growth factor-1 (IGF-1) and thrombopoietin (TPO), or the Gz-coupled receptor ligand epinephrine. We found that platelet primers largely overcame the inhibitory effects of antiplatelet compounds on platelet functional responses. IGF-1-mediated and TPO-mediated, but not epinephrine-mediated, enhancements in the presence of antiplatelet drugs were blocked by the PI3K inhibitors wortmannin and LY294002.ConclusionsThese results demonstrate that platelet primers can contribute to antiplatelet resistance. Furthermore, our data demonstrate that there are PI3K-dependent and PI3K-independent mechanisms driving primer-mediated resistance to antiplatelet therapy.
| S-EPMC4599128 | biostudies-literature
Project description:Platelet mRNA in response to antiplatelet therapy exposure
| PRJNA666442 | ENA
Project description:Objectives: Diabetes mellitus (DM) is a significant risk factor for ischemic stroke and associated with platelet reactivity. We aim to evaluate the effect of DM on platelet function in acute ischemic stroke patients taking dual antiplatelet therapy (DAPT). Methods: We consecutively included patients with acute ischemic stroke taking DAPT. Platelet function was assessed by thromboelastography and the arachidonic acid (AA) or adenosine diphosphate (ADP) induced platelet inhibition rate were used to confirmed the high-residual on-treatment platelet reactivity (HRPR) to aspirin or clopidogrel. We classified patients into DM and non-DM groups. The association between DM and platelet function was assessed and the confounding factors were adjusted by propensity score matching (PSM) analysis. The independent risk factors of HRPR were determined by multivariate logistic regression analysis. Results: A total of 1,071 acute ischemic stroke patients, 712 in the non-DM group and 359 in the DM group, were included. Patients with DM had a significantly higher maximum amplitude (63.0 vs. 62.0 mm, P < 0.01), ADP-induced clot strength (34.6 vs. 30.3 mm, P < 0.01) and clopidogrel HRPR rate (22.6% vs. 17.3%, P = 0.038) than those without DM. Among 662 patients after PSM, the maximum amplitude (63.1 vs. 62.5 mm, P = 0.032), ADP-induced clot strength (34.6 vs. 29.3 mm, P < 0.01) and clopidogrel HRPR rate (23.0% vs. 15.7%, P = 0.018) is still higher in the DM group. DM was an independent factor of clopidogrel HRPR (OR = 1.48, 95% CI: 1.03-2.07, P < 0.05). Conclusions: In acute ischemic stroke patients taking DAPT, DM is associated with increased platelet reactivity and higher prevalence of clopidogrel HRPR.
| S-EPMC8599121 | biostudies-literature
Project description:Patients with CKD display a significantly higher risk of cardiovascular and thromboembolic complications, with around half of patients with advanced CKD ultimately dying of cardiovascular disease. Paradoxically, these patients also have a higher risk of hemorrhages, greatly complicating patient therapy. Platelets are central to hemostasis, and altered platelet function resulting in either platelet hyper- or hyporeactivity may contribute to thrombotic or hemorrhagic complications. Different molecular changes have been identified that may underlie altered platelet activity and hemostasis in CKD. In this study, we summarize the knowledge on CKD-induced aberrations in hemostasis, with a special focus on platelet abnormalities. We also discuss how prominent alterations in vascular integrity, coagulation, and red blood cell count in CKD may contribute to altered hemostasis in these patients who are high risk. Furthermore, with patients with CKD commonly receiving antiplatelet therapy to prevent secondary atherothrombotic complications, we discuss antiplatelet treatment strategies and their risk versus benefit in terms of thrombosis prevention, bleeding, and clinical outcome depending on CKD stage. This reveals a careful consideration of benefits versus risks of antiplatelet therapy in patients with CKD, balancing thrombotic versus bleeding risk. Nonetheless, despite antiplatelet therapy, patients with CKD remain at high cardiovascular risk. Thus, deep insights into altered platelet activity in CKD and underlying mechanisms are important for the optimization and development of current and novel antiplatelet treatment strategies, specifically tailored to these patients who are high risk. Ultimately, this review underlines the importance of a closer investigation of altered platelet function, hemostasis, and antiplatelet therapy in patients with CKD.
| S-EPMC8763166 | biostudies-literature
Project description:Antiplatelet therapy is the most important treatment to reduce the risk of developing recurrent thrombosis, and to prevent progression to a complete occlusion of coronary arterial disease (CAD) patients after percutaneous coronary intervention Aim of study was to investigate the relationship between response to antiplatelet drugs and global mRNA gene expression in peripheral blood cells (PBC) in patients with coronary arterial disease (CAD) All patients were treated crhonically with acetylsalicylic acid (ASA) (100 mg/day) and clopidogrel (75 mg/day). Blood samples were drown before PCI to evaluate platelet reactivity by VerifyNow® ASA and P2Y12 assays and mRNA expression was measured by Affymetrix GeneChip Human Exon 1.0 ST array.
2012-09-15 | E-GEOD-32226 | biostudies-arrayexpress
Project description:Background and purposeGrowing evidence of the relationship between poor antiplatelet response and occurrence of clinical events elicited the need of monitoring the response which has not been part of our daily practice. We present our initial experience with a new point-of-care antiplatelet-function test (VerifyNow assay) in neurointerventional procedures.Materials and methodsAmong the 106 consecutive patients from July 2006 to April 2007, ninety-eight met the inclusion criteria. Our preferred antiplatelet regimen was aspirin (325 mg daily) and clopidogrel (300 mg of loading dose followed by 75 mg daily) starting 5-10 days before the procedure. The test results were reported as aspirin-reaction unit (ARU) for aspirin and P2Y(12) reaction units (PRU), baseline (BASE), and percentage inhibition for the P2Y(12) assay and were summarized as mean +/- SD of the values. We analyzed the effects of several factors of poor clopidogrel response (<40% inhibition). The occurrence of thrombotic events was recorded.ResultsThe mean ARU of aspirin assays was 438.3 +/- 47.9 (range, 350-632), and the response was poor in 2 patients (2.1%). For clopidogrel, the mean of the BASE, PRU, and percentage inhibition was 356.8 +/- 56.3 (range, 234-495), 198.9 +/- 104.4 (range, 8-401), and 45.2 +/- 27.1% (range, 0-98), respectively. Forty-two patients (42.9%) showed poor response. Multivariate analysis showed greater body weight (81.9 Kg +/- 19.1 kg versus 69.9 +/- 15 kg) in the poor-response group. All 3 cases of intraprocedural thrombosis (3.1%) were observed only in the poor-response group.ConclusionWe observed a high frequency of poor clopidogrel responses in the neurointerventional setting. Routine monitoring of the drug response would be helpful for the early identification of poor antiplatelet responders so that we may modify the regimen and/or treatment plan.
| S-EPMC8119128 | biostudies-literature