Table 1.
Studies investigating the association between platelet and/or circulatory miRNA levels and platelet activation.
| Evidence | Reference | Year | miRNAs of Interest | Agonist/Condition/Treatment | PFT | Origin of Samples | Method |
|---|---|---|---|---|---|---|---|
| B | [14] | 2011 | 74 miRNAs differentially expressed | Hyperreactive vs. hyporeactive platelets | Maximal aggregation response to ADP and epinephrine | 19 healthy subjects | S |
| B | [31] | 2011 | miR-15a miR-98 miR-339 miR-361 miR-365 miR-495 | Thrombin | P-selectin | 4 stimulated, 6 resting platelet samples from healthy subjects | S |
| A + B + D | [75] | 2012 | miR-1246 miR-451 miR-223 miR-146 miR-133 miR-126 miR-21 miR-19 | ADP and patients with stable CAD vs. patients with ACS | - | Extracted platelets, 5 patients with stable CAD, 5 patients with ACS | T |
| A + B + D | [79] | 2012 | miR-223 miR-197 miR-126 miR-24 miR-21 | Thrombin and healthy subjects: limb ischemia-reperfusion | - | 820 subjects from general population (Bruneck cohort), 11 healthy subjects, extracted platelets and PMVs | S + T |
| A + B D + E | [71] | 2013 | miR-223 miR-197 miR-191 miR-150 miR-126 miR-24 miR-21 miR-20b | Healthy subjects: dose-escalation of ASA combined with prasugrel Patients: ASA at baseline, addition of dipyridamole or clopidogrel | Verify Now, LTA, formation of thromboxane B2 | Platelets, PMVs, serum, PRP, PPP from 3 healthy subjects, serum and PPP from 19 T2DM patients, 9 healthy subjects, 33 patients with symptomatic carotid atherosclerosis | S + T |
| B + E | [80] | 2013 | miR-223 miR-96 | Clopidogrel + ASA | VASP assay, LTA | 33 non-diabetic CVD patients | T |
| A + C | [77] | 2013 | miR-223 | Thrombin and co-incubation of HUVECs with released PMVs | P-selectin | Extracted platelets, HUVEC | T |
| A + D + E | [81] | 2013 | miR-126 | PRP stimulated with AA in presence/absence of aspirin and patients: one period (6 weeks) placebo, one period ASA | P-selectin | 4 healthy subjects, 40 T2DM patients without CVD | T |
| E | [82] | 2014 | miR-223 | DAPT with clopidogrel | VASP assay | 62 ACS patients | T |
| B | [83] | 2015 | ~50 miRNAs differentially expressed | ADP, collagen, TRAP | LTA | 15 healthy subjects | S |
| D | [49] | 2015 | miR-223 | T2DM | Clot retraction & platelet adhesion and spreading assay | 22 patients with T2DM, 22 healthy subjects | T |
| E | [84] | 2015 | miR-223 | DAPT with clopidogrel or prasugrel or ticagrelor | MEA | 21 patients with ACS | T |
| D + E | [52] | 2016 | miR-223 miR-191 miR-126 miR-24 | Healthy subjects: DAPT with prasugrel and patients: ASA only or DAPT with clopidogrel, prasugrel, or ticagrelor | VASP assay, LTA, Verify Now | 669 subjects from general population (Bruneck cohort), 125 ACS patients, additional ACS patients (n = 8/group) and healthy subjects (n = 6) to assess impact of antiplatelet treatment | S |
| C | [47] | 2016 | miR-126 | Thrombin stimulation of platelets, co-incubation of PMVs with primary human macrophages | - | Healthy subjects | S + T |
| E | [85] | 2016 | miR-223 miR-150 miR-126 miR-96 | Switch from DAPT with clopidogrel to ticagrelor “No load”: ASA + ticagrelor without LD“Load”: ticagrelor LD, then ticagrelor MD + ASA |
MEA | 16 ACS patients (8 “no load” group, 8 “load” group) | T |
| E | [86] | 2017 | miR-223 miR-221 miR-21 | DAPT with clopidogrel | LTA | 272 subjects included; 21 “high responders”, 18 “low responders” | T |
| A | [36] | 2018 | 46 miRNAs consistently secreted | CRP-XL, PAR1-AP, PAR4-AP, ADP | - | 4 healthy subjects | S |
| E | [87] | 2019 | miR-223 miR-150 miR-126 miR-21 | Cessation of DAPT with clopidogrel or prasugrel or ticagrelor | MEA | 62 CAD patients | T |
| E | [88] | 2020 | miR-223 miR-197 miR-191 miR-24 | ASA + one period (28 days) clopidogrel, one period prasugrel | LTA, P-selectin | 56 T2DM patients | T |
| E | [89] | 2020 | miR-223 miR-150 miR-130 miR-126 | Patients: ASA + clopidogrel | TEG | 214 healthy subjects, 430 ACS patients | T |
(A) The secretion of miRNAs into buffer and plasma, (B) alterations of the intracellular platelet miRNome, (C) alterations of miRNA levels in cells after (presumable) uptake of platelet-derived miRNAs, (D) alterations in miRNA levels linked to diseases known to be associated with increased platelet activation (such as CVDs), and (E) alterations of miRNA levels upon antiplatelet therapy. (S = screening (NGS, microarray, high-throughput qPCR), T = targeted approach (individual qPCRs)). AA = arachidonic acid, ACS = acute coronary syndrome, ADP = adenosine diphosphate, ASA = acetylsalicylic acid (aspirin), CAD = coronary artery disease, CRP-XL = crosslinked collagen-related peptide, DAPT = dual antiplatelet therapy, HUVEC= human umbilical vein endothelial cell, LD = loading dose, LTA = light transmission aggregometry, MD = maintenance dose, MEA = multiple electrode aggregometry, PAR2-AP = protease-activated receptor-2 activating peptide, PAR4-AP = protease-activated receptor-4 activating peptide, PMV = platelet microvesicle, PPP = platelet-poor plasma, PRP = platelet-rich plasma, T2DM = type 2 diabetes mellitus, TEG = thromboelastography, TRAP = thrombin receptor activating peptide, VASP = vasodilator-stimulated phosphoprotein phosphorylation.