학술논문
Ticagrelor downregulates the expression of proatherogenic and proinflammatory miR125-b compared to clopidogrel: A randomized, controlled trial.
Document Type
Academic Journal
Author
Gasecka A; 1(st) Chair and Department of Cardiology, Medical University of Warsaw, Warsaw, Poland. Electronic address: aleksandra.gasecka@wum.edu.pl.; Błażejowska E; 1(st) Chair and Department of Cardiology, Medical University of Warsaw, Warsaw, Poland.; Pluta K; Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology, Medical University of Warsaw, Warsaw, Poland.; Gajewska M; 1(st) Chair and Department of Cardiology, Medical University of Warsaw, Warsaw, Poland.; Rogula S; 1(st) Chair and Department of Cardiology, Medical University of Warsaw, Warsaw, Poland.; Filipiak KJ; Maria Sklodowska-Curie Medical Academy in Warsaw, Warsaw, Poland; Department of Hypertensiology, Angiology and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland.; Kochman J; 1(st) Chair and Department of Cardiology, Medical University of Warsaw, Warsaw, Poland.; Siller-Matula JM; Department of Cardiology, Medical University of Vienna, Vienna, Austria.; Postuła M; Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology, Medical University of Warsaw, Warsaw, Poland.; Eyileten C; Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology, Medical University of Warsaw, Warsaw, Poland.
Source
Publisher: Elsevier Country of Publication: Netherlands NLM ID: 8200291 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1874-1754 (Electronic) Linking ISSN: 01675273 NLM ISO Abbreviation: Int J Cardiol Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Platelet P2Y12 antagonist ticagrelor reduces cardiovascular mortality after acute myocardial infarction (AMI) compared to clopidogrel, but the underlying mechanism is unknown. Because activated platelets release proatherogenic and proinflammatory microRNAs, including miR-125a, miR-125b and miR-223, we hypothesized that the expression of these miRNAs is lower on ticagrelor, compared to clopidogrel.
Objectives: We compared miR-125a, miR-125b and miR-223 expression in plasma of patients after AMI treated with ticagrelor or clopidogrel.
Methods: After percutaneous coronary intervention on acetylsalicylic acid and clopidogrel, 60 patients with first AMI were randomized to switch to ticagrelor or to continue with clopidogrel. Plasma expression of miR-223, miR-125a-5p, miR-125b was measured using quantitative polymerase chain reaction at baseline and after 72 h and 6 months of treatment with ticagrelor or clopidogrel in patients and one in 30 healthy volunteers. Multiple electrode aggregometry using ADP test was used to determine platelet reactivity in response to P2Y12 inhibitors.
Results: Expression of miR-125b was higher in patients with AMI 72 h and 6 months, compared to healthy volunteers (p = 0.001), whereas expression of miR-125a-5p and miR-223 were comparable. In patients randomized to ticagrelor, expression of miR-125b decreased at 72 h (p = 0.007) and increased back to baseline at 6 months (p = 0.005). Expression of miR-125a-5p and miR-223 was not affected by the switch from clopidogrel to ticagrelor.
Conclusions: Ticagrelor treatment leads to lower plasma expression of miR-125b after AMI, compared to clopidogrel. Higher expression of miR-125b might explain recurrent thrombotic events and worse clinical outcomes in patients treated with clopidogrel, compared to ticagrelor.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Objectives: We compared miR-125a, miR-125b and miR-223 expression in plasma of patients after AMI treated with ticagrelor or clopidogrel.
Methods: After percutaneous coronary intervention on acetylsalicylic acid and clopidogrel, 60 patients with first AMI were randomized to switch to ticagrelor or to continue with clopidogrel. Plasma expression of miR-223, miR-125a-5p, miR-125b was measured using quantitative polymerase chain reaction at baseline and after 72 h and 6 months of treatment with ticagrelor or clopidogrel in patients and one in 30 healthy volunteers. Multiple electrode aggregometry using ADP test was used to determine platelet reactivity in response to P2Y12 inhibitors.
Results: Expression of miR-125b was higher in patients with AMI 72 h and 6 months, compared to healthy volunteers (p = 0.001), whereas expression of miR-125a-5p and miR-223 were comparable. In patients randomized to ticagrelor, expression of miR-125b decreased at 72 h (p = 0.007) and increased back to baseline at 6 months (p = 0.005). Expression of miR-125a-5p and miR-223 was not affected by the switch from clopidogrel to ticagrelor.
Conclusions: Ticagrelor treatment leads to lower plasma expression of miR-125b after AMI, compared to clopidogrel. Higher expression of miR-125b might explain recurrent thrombotic events and worse clinical outcomes in patients treated with clopidogrel, compared to ticagrelor.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)