A MicroRNA Signature in Acute Coronary Syndrome Patients and Modulation by Colchicine.

Autor:	Barraclough JY; Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia.; Sydney Medical School, The University of Sydney, Australia.; Heart Research Institute Sydney, Australia., Joglekar MV; NHMRC Clinical Trials Centre, Faculty of Medicine and Health, The University of Sydney, Australia., Januszewski AS; NHMRC Clinical Trials Centre, Faculty of Medicine and Health, The University of Sydney, Australia., Martínez G; Heart Research Institute Sydney, Australia.; Division of Cardiovascular Diseases, Pontificia Universidad Católica de Chile, Santiago, Chile., Celermajer DS; Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia.; Sydney Medical School, The University of Sydney, Australia.; Heart Research Institute Sydney, Australia., Keech AC; Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia.; NHMRC Clinical Trials Centre, Faculty of Medicine and Health, The University of Sydney, Australia., Hardikar AA; NHMRC Clinical Trials Centre, Faculty of Medicine and Health, The University of Sydney, Australia., Patel S; Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia.; Sydney Medical School, The University of Sydney, Australia.; Heart Research Institute Sydney, Australia.
Jazyk:	angličtina
Zdroj:	Journal of cardiovascular pharmacology and therapeutics [J Cardiovasc Pharmacol Ther] 2020 Sep; Vol. 25 (5), pp. 444-455. Date of Electronic Publication: 2020 May 01.
DOI:	10.1177/1074248420922793
Abstrakt:	Background: Circulating microRNAs (miRNAs) may play a pathogenic role in acute coronary syndromes (ACS). It is not yet known if miRNAs dysregulated in ACS are modulated by colchicine. We profiled miRNAs in plasma samples simultaneously collected from the aorta, coronary sinus, and right atrium in patients with ACS. Methods: A total of 396 of 754 miRNAs were detected by TaqMan real-time polymerase chain reaction from EDTA-plasma in a discovery cohort of 15 patients (n = 3 controls, n = 6 ACS standard therapy, n = 6 ACS standard therapy plus colchicine). Fifty-one significantly different miRNAs were then measured in a verification cohort of 92 patients (n = 13 controls, n = 40 ACS standard therapy, n = 39 ACS standard therapy plus colchicine). Samples were simultaneously obtained from the coronary sinus, aortic root, and right atrium. Results: Circulating levels of 30 of 51 measured miRNAs were higher in ACS standard therapy patients compared to controls. In patients with ACS, levels of 12 miRNAs (miR-17, -106b-3p, -191, -106a, -146a, -130a, -223, -484, -889, -425-3p, -629, -142-5p) were lower with colchicine treatment. Levels of 7 of these 12 miRNA were higher in ACS standard therapy patients compared to controls and returned to levels seen in control individuals after colchicine treatment. Three miRNAs suppressed by colchicine (miR-146a, miR-17, miR-130a) were identified as regulators of inflammatory pathways. MicroRNAs were comparable across sampling sites with select differences in the transcoronary gradient of 4 miRNA. Conclusion: The levels of specific miRNAs elevated in ACS returned to levels similar to control individuals following colchicine. These miRNAs may mediate ACS (via inflammatory pathways) or increase post-ACS risk, and could be potentially used as biomarkers of treatment efficacy.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu