Interaction between platelet-derived microRNAs and CYP2C19*2 genotype on clopidogrel antiplatelet responsiveness in patients with ACS

Li, Peng; Li, Jun; Qin, Liuan; Liu, Jia; Xi, Shaozhi; Lu, Caiyi; Yin, Tong

doi:10.1016/j.thromres.2017.07.011

Cited by 22 publications

(40 citation statements)

References 39 publications

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“…In 121 patients with a history of acute coronary syndrome, plasma levels of miR-223, miR-197, miR-191 and miR-24 showed significant positive correlations with the vasodilator-stimulated phosphoprotein phosphorylation assay but not light transmittance aggregometry tests after 30 days of dual antiplatelet therapy [29]. In contrast to our results, studies using platelet-rich or platelet-poor plasma from patients with acute coronary syndrome found miR-223 levels to be decreased in patients with a very low response to P2Y 12 inhibitors, compared with normal responders [30][31][32]. Differences in sample preparation and normalization, as well as potential interference of heparin [33], can all substantially affect measurements of circulating miRNAs [21].…”

Section: Discussioncontrasting

confidence: 99%

Circulating MicroRNA Levels Indicate Platelet and Leukocyte Activation in Endotoxemia Despite Platelet P2Y12 Inhibition

Braza-Boïls

Barwari

Gutmann

et al. 2020

IJMS

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There is evidence for the effects of platelet inhibition on innate immune activation. Circulating microRNAs (miRNAs) have been implicated as markers of platelet and leukocyte activation. In the present study, we assessed the effects of P2Y 12 inhibitors on platelet and leukocyte miRNAs during endotoxemia. Healthy volunteers were randomly assigned to receive oral ticagrelor (n = 10), clopidogrel (n = 8) or no drug (n = 8) for one week, followed by an intravenous bolus of 2 ng/kg endotoxin. Serum was collected at baseline, after one week of antiplatelet treatment and 6 and 24 h after endotoxin administration. MiRNAs were screened using LNA-based qPCR, followed by TaqMan-qPCR validation of candidates. Clinical validation was performed in 41 sepsis patients. Platelet-enriched miR-197, miR-223 and miR-223* were decreased in volunteers following antiplatelet therapy. Endotoxin increased platelet miRNAs, whilst the opposite effect was seen for leukocyte-enriched miR-150. Neither of these endotoxin-mediated effects were altered by P2Y 12 inhibitors. Sepsis patients with fatal outcomes (n = 12) had reduced miR-150 levels compared with survivors (n = 29). In conclusion, we show that miR-150 is downregulated in experimental endotoxemia and can predict survival in sepsis but is unaffected by P2Y 12 inhibition. While P2Y 12 inhibition reduces platelet-associated miRNAs in healthy volunteers, it fails to attenuate the response of platelet miRNAs to endotoxemia.

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Section: Discussioncontrasting

confidence: 99%

Circulating MicroRNA Levels Indicate Platelet and Leukocyte Activation in Endotoxemia Despite Platelet P2Y12 Inhibition

Braza-Boïls

Barwari

Gutmann

et al. 2020

IJMS

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“…52 This correlation between miR-223 and platelet responsiveness was confirmed by several other studies. 32,53,54 Similarly, several other platelet miRs were reported to correlate with ontreatment platelet reactivity, including miR-126, miR-92a, miR-26a, and miR-365-3p. 32,[55][56][57] MiR-126 and miR-223 showed strong correlation with platelet function tests in plasma of patients on dual antiplatelet therapy 1 month after ACS.…”

Section: Platelets Micrornas In Antiplatelet Drug Resistancementioning

confidence: 97%

“…32 Three platelet-related miRs, miR-223, miR-221, and miR-21, were associated with platelet responsiveness on clopidogrel treatment in platelets of carriers of CYP2C19 Ã 2 genotype following ACS and discriminate high and low responders on clopidogrel treatment. 54 After therapeutic switch from clopidogrel to ticagrelor, expression of miR-126, miR-223, and miR-150 in plasma decreases, whereas the expression of miR-96 increases. 58 In addition, miR-126 expression was further decreased in plasma from patients with ticagrelor loading as compared with patients without loading dose, suggesting that miR-126 expression decreases with increasing intensity of platelet inhibition.…”

Section: Platelets Micrornas In Antiplatelet Drug Resistancementioning

confidence: 99%

MicroRNAs as Regulators and Biomarkers of Platelet Function and Activity in Coronary Artery Disease

et al. 2019

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Microribonucleic acids (miRs) are small, noncoding ribonucleic acids (RNAs), which play an important role in the regulation of platelet function and activity. Several studies proposed a mechanistic role of platelet-related miRs in the pathophysiology of coronary artery disease (CAD) and atherothrombosis. Circulating, platelet-related miRs have been proposed as diagnostic, prognostic, as well as treatment response biomarkers in CAD and acute coronary syndrome (ACS). In this review, we summarize recent studies on the role of platelet-related miRs in the regulation of platelet function and activity. Furthermore, we review the studies investigating the role of platelet-related miRs as biomarkers in patients with CAD and ACS.

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“…Previous findigs have confirmed that ( 13 ) CYP2C19 gene polymorphism is a major factor affecting the anti-platelet effect of clopidogrel. CYP2C19-2 and CYP2C19-3 are PM subtypes of CYP2C19 ( 14 ), which are mainly expressed in Asian populations ( 15 ) with higher mutation rates ( 16 ); thus, the incidence rate of severe cardiovascular complications is increased significantly in PM subjects ( 17 ). The long-term application of clopidogrel in patients complicated with atrial fibrillation after PCI should be paid attention to ( 18 ); the anti-platelet therapy regimen should be adjusted in time ( 19 ) to avoid stent thrombosis-induced complications ( 20 ).…”

Section: Discussionmentioning

confidence: 99%

Effects of different CYP2C19 genotypes on prognosis of patients complicated with atrial fibrillation taking clopidogrel after PCI

Zhang

Zhong

et al. 2018

Exp Ther Med

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The effects of different cytochrome P450 2C19 (CYP2C19) genotypes on the prognosis of clopidogrel resistance in patients complicated with atrial fibrillation taking clopidogrel after percutaneous coronary intervention (PCI) were investigated. Eighty patients who were complicated with atrial fibrillation and treated with clopidogrel antiplatelet therapy after PCI in Meizhou Hospital Affiliated to Zhongshan University from September 2015 to January 2017 were selected, and divided into two groups according to the CYP2C19 genotype: extensive metabolism (EM) group and poor metabolism (PM) group. The related risk factors of clopidogrel resistance were determined, and the platelet aggregation rate and clopidogrel resistance rate were compared between the two groups during treatment. Non-fatal myocardial infarction and serious life-threatening complications in the two groups were observed. The increased total cholesterol level and the history of smoking and drinking were the independent risk factors of atrial fibrillation after PCI. The platelet aggregation rates in the EM group at 1, 3 and 12 months after medication were significantly lower than those in the PM group in the same period (P<0.05). The clopidogrel resistance rates in EM group before medication and at 1, 3 and 12 months after medication were higher than those in PM group in the same period (P<0.05). The onset time of non-fatal myocardial infarction in EM group was earlier than that in PM group (P<0.05), the infarct area was larger than that in PM group (P<0.05), and the left ventricular ejection fraction (EF) after onset was lower than that in PM group (P<0.05). In conclusion, the increased total cholesterol level and the history of smoking and drinking are the independent risk factors of clopidogrel resistance in patients complicated with atrial fibrillation after PCI. The incidence rates of cardiac complications are increased significantly in patients with PM CYP2C19 genotype.

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Interaction between platelet-derived microRNAs and CYP2C19*2 genotype on clopidogrel antiplatelet responsiveness in patients with ACS

Cited by 22 publications

References 39 publications

Circulating MicroRNA Levels Indicate Platelet and Leukocyte Activation in Endotoxemia Despite Platelet P2Y12 Inhibition

Circulating MicroRNA Levels Indicate Platelet and Leukocyte Activation in Endotoxemia Despite Platelet P2Y12 Inhibition

MicroRNAs as Regulators and Biomarkers of Platelet Function and Activity in Coronary Artery Disease

Effects of different CYP2C19 genotypes on prognosis of patients complicated with atrial fibrillation taking clopidogrel after PCI

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