Circulating MicroRNAs and Monocyte–Platelet Aggregate Formation in Acute Coronary Syndrome

Abstract

Background Monocyte–platelet aggregates (MPAs) are a sensitive marker of in vivo platelet activation in acute coronary syndrome (ACS) and associated with clinical outcomes. MicroRNAs (miRs) play an important role in the regulation of platelet activation, and may influence MPA formation. Both, miRs and MPA, could be influenced by the type of P2Y12 inhibitor. Aim To study the association of platelet-related miRs with MPA formation in ACS patients on dual antiplatelet therapy (DAPT), and to compare miRs and MPA levels between prasugrel- and ticagrelor-treated patients. Methods and Results We analyzed 10 circulating platelet-related miRs in 160 consecutive ACS patients on DAPT with low-dose aspirin and either prasugrel (n = 80) or ticagrelor (n = 80). MPA formation was measured by flow cytometry without addition of platelet agonists and after simulation with the toll-like receptor (TLR)-1/2 agonist Pam3CSK4, adenosine diphosphate (ADP), or arachidonic acid (AA). In multivariate regression analyses, we identified miR-21 (β = 9.50, 95% confidence interval [CI]: 1.60–17.40, p = 0.019) and miR-126 (β = 7.50, 95% CI: 0.55–14.44, p = 0.035) as independent predictors of increased MPA formation in vivo and after TLR-1/2 stimulation. In contrast, none of the investigated miRs was independently associated with MPA formation after stimulation with ADP or AA. Platelet-related miR expression and MPA formation did not differ significantly between prasugrel- and ticagrelor-treated patients. Conclusion Platelet-related miR-21 and miR-126 are associated with MPA formation in ACS patients on DAPT. miRs and MPA levels were similar in prasugrel- and ticagrelor-treated patients.

MicroRNAs in Kawasaki disease: An update on diagnosis, therapy and monitoring

“…later compared the ratio of miR-126a between aspirin treatment patients and non-responders, and the results revealed that the level of miR-126a decreased after aspirin treatment ( 124 ). Furthermore, cessation of miRNAs, including miRNA-223, miRNA-21, miRNA-150, and miRNA-126, are associated with the regulation of the P2Y12 receptor and thus affect platelet aggregation ( 125 – 127 ). Zhang et al.…”

Thrombosis and Haemostasis 2021 Editors' Choice Papers

“…The study from Stojkovic et al assessing the relationship between different circulating miRNAs and monocyte-platelet aggregate formation in patients with acute coronary syndrome on dual antiplatelet therapy is an example of such new interest. 96 Garcia et al identified an important role of a specific miRNA, miR-204-5p, on in vitro platelet production and function, 97 suggesting genetic control of platelet production and function by miR-204-5p which may thus be considered as a new biomarker for high platelet reactivity in the context of personalized antiplatelet therapy. 98 The comprehensive overview of currently available techniques for studying miRNA function with a focus on platelet reactivity regulation by Garcia et al, 99 also attracted much interest among our author community seeking to overcome the current methodological limitations in this field.…”

MiR-126 Is an Independent Predictor of Long-Term All-Cause Mortality in Patients with Type 2 Diabetes Mellitus

“…We aimed to determine the prognostic performance of selected circulating miRNAs for all-cause mortality and their potential usefulness as biomarkers in T2DM patients on antiplatelet treatment. Several studies showed the role of miR-126 and miR-223 in the context of antiplatelet treatment in many different cohorts [ 16 , 19 , 20 , 21 , 22 , 23 ]. Changes in plasma miRNAs in response to antiplatelet therapy were investigated in a small cohort of healthy volunteers [ 16 , 19 , 20 , 21 , 22 , 23 ].…”

“…Yu et al analyzed the correlation between plasma miR-126 and miR-223, among others, and the risk of major adverse cardiovascular events in patients on dual antiplatelet therapy (DAPT) after percutaneous coronary intervention [ 16 , 19 , 20 , 21 , 22 , 23 ]. The association between miRNAs and platelet reactivity was also studied in patients with acute coronary syndrome (ACS) on various antiplatelet therapies [ 16 , 19 , 20 , 21 , 22 , 23 ]. In a similar study Carino et al assessed miR-126 and miR-223, among other miRNAs, in patients with ACS before and after the therapeutic switch from DAPT to ticagrelor [ 16 , 19 , 20 , 21 , 22 , 23 ].…”

“…In a similar study Carino et al assessed miR-126 and miR-223, among other miRNAs, in patients with ACS before and after the therapeutic switch from DAPT to ticagrelor [ 16 , 19 , 20 , 21 , 22 , 23 ]. More recently the association of platelet-related miRNAs was studied in ACS patients on DAPT and pathophysiological processes in the TDM population [ 16 , 19 , 20 , 21 , 22 , 23 ]. Among others, Let-7e and miR-125a-3p are molecules that have been formerly linked to inflammation, platelet reactivity, and mechanisms leading to diabetes; however, the impact of antiplatelet therapy on Let-7e and miR-125a-3p and their prognostic potential has not been studied so far [ 24 , 25 , 26 ].…”