TY - JOUR
T1 - Serum microRNAs and antifibrotic response to eplerenone in acute myocardial infarction complicated by systolic dysfunction
AU - Stienen, Susan
AU - Ferreira, João Pedro
AU - Bär, Christian
AU - Thum, Thomas
AU - Barros, António
AU - Pitt, Bertram
AU - Girerd, Nicolas
AU - Rossignol, Patrick
AU - Zannad, Faiez
N1 - Funding Information: The EPHESUS trial was sponsored by Pfizer. BP, JM and FZ were members of the steering committees. BP is a consultant for Bayer, Astra Zeneca, Sanofi, KBP Biosciences*, Sarfez*, Relypsa/ Vifor*, Tricida*, Stealth Peptides.* = stock options. He holds a patent for site-specific delivery of eplerenone to the myocardium (US patent # 9931412). All other authors have no conflicts of interest to declare.SS, JF, FZ and PR are supported by a public grant overseen by the French National Research Agency (ANR) as part of the second ?Investissements d'Avenir? program FIGHT-HF (reference: ANR-15-RHU-0004) and by the French PIA project ?Lorraine Universit? d'Excellence?, reference ANR-15-IDEX-04-LUE, and by the Contrat de plan Etat-lorraine and FEDER lorraine. SS received funding from the European Society of Cardiology in form of an ESC Research Grant (R-2018-18686). TT was supported by the German Research Foundation (DFG Th903/18-1) and the ERANet Grant EXPERT (BMBF, Germany, research grant ERA-CVD JTC2016 EXPERT, 01KL1711). AB was supported by DOCnet (NORTE-01-0145-FEDER-000003), by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). Publisher Copyright: © 2021 Elsevier B.V. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/6/1
Y1 - 2021/6/1
N2 - Background: After myocardial infarction (MI) complicated by heart failure (HF), eplerenone reduced serum concentrations of amino-terminal propeptide of type III collagen (PIIINP) and carboxy-terminal propeptide of type I collagen (PICP). Determining a subgroup who are more prone to decrease their collagen content and to respond better to the antifibrotic effects of mineralocorticoid receptor antagonists (MRA) may be relevant for a personalized treatment approach. Whether circulating microRNAs may identify a subgroup that have experienced a more pronounced antifibrotic effect of eplerenone as measured by a PICP and PIIINP decrease is unclear. Methods: A set of circulating microRNAs linked to cardiac fibrosis (mir-1, mir-21, mir-29a, mir-29b, mir-101, mir-122, mir-133a) were measured at baseline in 198 patients in the biomarker substudy of Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). Associations between baseline microRNA levels and changes in both PIIINP and PICP from baseline to month 9 were studied using multivariable analysis of covariance, adjusting for age, sex, history of hypertension and diabetes mellitus, prescription of ACE-inhibitors or angiotensin receptor blockers, baseline PIIINP or PICP, and eplerenone treatment. Furthermore, a treatment-by-microRNA interaction was studied. Results: From the selected microRNAs, only mir-133a was associated with a PICP decrease (ß-6.43, 95%CI-12.71 to −0.15,p = 0.045). None of the microRNAs was associated with a PIIINP change. The microRNAs did not predict an effect of eplerenone on PICP and PIIINP changes. Conclusion: Although serum mir-133a was associated with PICP change, none of the microRNAs previously linked to cardiac fibrosis predicted an antifibrotic response to eplerenone. Further study is needed to identify other suitable targets for a personalized treatment approach.
AB - Background: After myocardial infarction (MI) complicated by heart failure (HF), eplerenone reduced serum concentrations of amino-terminal propeptide of type III collagen (PIIINP) and carboxy-terminal propeptide of type I collagen (PICP). Determining a subgroup who are more prone to decrease their collagen content and to respond better to the antifibrotic effects of mineralocorticoid receptor antagonists (MRA) may be relevant for a personalized treatment approach. Whether circulating microRNAs may identify a subgroup that have experienced a more pronounced antifibrotic effect of eplerenone as measured by a PICP and PIIINP decrease is unclear. Methods: A set of circulating microRNAs linked to cardiac fibrosis (mir-1, mir-21, mir-29a, mir-29b, mir-101, mir-122, mir-133a) were measured at baseline in 198 patients in the biomarker substudy of Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). Associations between baseline microRNA levels and changes in both PIIINP and PICP from baseline to month 9 were studied using multivariable analysis of covariance, adjusting for age, sex, history of hypertension and diabetes mellitus, prescription of ACE-inhibitors or angiotensin receptor blockers, baseline PIIINP or PICP, and eplerenone treatment. Furthermore, a treatment-by-microRNA interaction was studied. Results: From the selected microRNAs, only mir-133a was associated with a PICP decrease (ß-6.43, 95%CI-12.71 to −0.15,p = 0.045). None of the microRNAs was associated with a PIIINP change. The microRNAs did not predict an effect of eplerenone on PICP and PIIINP changes. Conclusion: Although serum mir-133a was associated with PICP change, none of the microRNAs previously linked to cardiac fibrosis predicted an antifibrotic response to eplerenone. Further study is needed to identify other suitable targets for a personalized treatment approach.
UR - http://www.scopus.com/inward/record.url?scp=85102474771&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ijcard.2021.02.088
DO - https://doi.org/10.1016/j.ijcard.2021.02.088
M3 - Article
C2 - 33676945
SN - 0167-5273
VL - 332
SP - 35
EP - 37
JO - International journal of cardiology
JF - International journal of cardiology
ER -