Low miR-19b-1-5p expression in isolated platelets after aspirin use is related to aspirin insensitivity

Kok, Maayke G.M.; Mandolini, Claudia; Moerland, Perry D.; Ronde, Maurice W J de; Sondermeijer, Brigitte M.; Halliani, Amalia; Nieuwland, Rienk; Cipollone, Francesco; Creemers, Esther E.; Meijers, Joost C. M.; Pinto-Sietsma, S.J.

doi:10.1016/j.ijcard.2015.10.098

Cited by 25 publications

(19 citation statements)

References 7 publications

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“…Plasma levels of this miRNA have been reported to change after treatment with aspirin (de Boer et al 2013) or aspirin and prasugrel (Zampetaki et al 2012). Similar observations have also been made for miR-223 (Shi et al 2013(Shi et al , 2015, while low miR-19b-1-5p expression was linked to aspirin insensitivity in platelets (Kok et al 2015).…”

Section: Next Stop: Epigeneticssupporting

confidence: 81%

Pharmacogenomics of Antiplatelet Drugs

Cerletti

Izzi

Iacoviello

et al. 2017

Platelets in Thrombotic and Non-Thrombotic Disorders

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Pharmacogenomics might contribute to the individual response variability to antiplatelet drugs (particularly aspirin and clopidogrel) in patients with ischemic coronary or cerebral vascular disease in terms of both therapeutic and adverse effects. Over the last two decades, a large number of studies and several meta-analyses on the possible genomic regulation of common "polygenic" ischemic cardio-and cerebrovascular diseases have been published. These studies have identified numerous DNA variants as disease or antiplatelet drug susceptibility markers. Some of these DNA variants confer a variable increase in risk for disease, while loss-of-function variants in the hepatic CYP2C19 system have been reported to be the predominant genetic mediators of clopidogrel and other thienopyridine drug antiplatelet response. However, the overall available data are still somewhat contradictory and do not yet allow to define a clear role for pharmacogenomics in providing effective, reliable, personalized antiplatelet therapy: neither clear conclusions nor definite guidelines are available on the clinical advantages of pharmacogenetic testing before prescribing antiplatelet drugs. In the near future, the relative role of additional rare polymorphisms, structural variants and tissue-specific epigenetic features of the human genome will hopefully be defined as significant contributors to the pathogenesis of cardio-and cerebrovascular disease and of individual patient's response to antiplatelet drugs.

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Section: Next Stop: Epigeneticssupporting

confidence: 81%

Pharmacogenomics of Antiplatelet Drugs

Cerletti

Izzi

Iacoviello

et al. 2017

Platelets in Thrombotic and Non-Thrombotic Disorders

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“…Several platelet miRNA related to CVD, such as miRNA-21 and miRNA-126, are significantly modulated in T2DM and studies are in progress to identify a miRNA-based signature associated with T2DM and its CVD complications [113]. Interestingly, platelet miRNA are responsive to antiplatelet therapy and may represent valid biomarker for the response to therapy as emerged in recent studies showing that aspirin resistance can potentially be identified by miR-92a and miR-19b-1-5p levels in plasma [114, 115]. Based on these observations, miRNA may become a valuable tool to provide diagnostic and prognostic information about T2DM, coronary artery disease complications and therapy responsiveness.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Platelets, diabetes and myocardial ischemia/reperfusion injury

Russo

Penna

Musso

et al. 2017

Cardiovasc Diabetol

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Mechanisms underlying the pathogenesis of ischemia/reperfusion injury are particularly complex, multifactorial and highly interconnected. A complex and entangled interaction is also emerging between platelet function, antiplatelet drugs, coronary diseases and ischemia/reperfusion injury, especially in diabetic conditions. Here we briefly summarize features of antiplatelet therapy in type 2 diabetes (T2DM). We also treat the influence of T2DM on ischemia/reperfusion injury and how anti-platelet therapies affect post-ischemic myocardial damage through pleiotropic properties not related to their anti-aggregating effects. miRNA-based signature associated with T2DM and its cardiovascular disease complications are also briefly considered. Influence of anti-platelet therapies and different effects of healthy and diabetic platelets on ischemia/reperfusion injury need to be further clarified in order to enhance patient benefits from antiplatelet therapy and revascularization. Here we provide insight on the difficulty to reduce the cardiovascular risk in diabetic patients and report novel information on the cardioprotective role of widely used anti-aggregant drugs.

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“…Pharmacogenetic studies have demonstrated an association between gene SNPs and aspirin non-response, but these associations are controversial (Maguire et al, 2008). Certain miRNA is associated with aspirin non-response, but the exact change in metabolic pathway is unclear (Kok et al, 2016). By examining metabolic alteration, key metabolites can be identified, and proposed causes of aspirin non-response may be validated.…”

Section: Discussionmentioning

confidence: 99%

Metabolomic Analysis of Platelets of Patients With Aspirin Non-Response

et al. 2019

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Background: Aspirin is the most commonly used antiplatelet agent for the prevention of cardiovascular diseases. However, a certain proportion of patients do not respond to aspirin therapy. The mechanisms of aspirin non-response remain unknown. The unique metabolomes in platelets of patients with coronary artery disease (CAD) with aspirin non-response may be one of the causes of aspirin resistance.Materials and Methods: We enrolled 29 patients with CAD who were aspirin non-responders, defined as a study subject who were taking aspirin with a platelet aggregation time less than 193 s by PFA-100, and 31 age- and sex-matched patients with CAD who were responders. All subjects had been taking 100 mg of aspirin per day for more than 1 month. Hydrophilic metabolites from the platelet samples were extracted and analyzed by nuclear magnetic resonance (NMR). Both 1D 1H and 2D J-resolved NMR spectra were obtained followed by spectral processing and multivariate statistical analysis, such as partial least squares discriminant analysis (PLS-DA).Results: Eleven metabolites were identified. The PLS-DA model could not distinguish aspirin non-responders from responders. Those with low serum glycine level had significantly shorter platelet aggregation time (mean, 175.0 s) compared with those with high serum glycine level (259.5 s). However, this association became non-significant after correction for multiple tests.Conclusions: The hydrophilic metabolic profile of platelets was not different between aspirin non-responders and responders. An association between lower glycine levels and higher platelet activity in patients younger than 65 years suggests an important role of glycine in the pathophysiology of aspirin non-response.

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Low miR-19b-1-5p expression in isolated platelets after aspirin use is related to aspirin insensitivity

Cited by 25 publications

References 7 publications

Pharmacogenomics of Antiplatelet Drugs

Pharmacogenomics of Antiplatelet Drugs

Platelets, diabetes and myocardial ischemia/reperfusion injury

Metabolomic Analysis of Platelets of Patients With Aspirin Non-Response

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