Profile of serum microRNAs in heart failure with reduced and preserved ejection fraction: Correlation with myocardial remodeling

Layde Rosane Paim; Luis Miguel da Silva; Lígia M Antunes-Correa; Vinicius Citelli Ribeiro; Roberto Schreiber; Eduarda O Z Minin; Larissa C M Bueno; Elisangela C P Lopes; Renan Yamaguti; Andréa Coy-Canguçu; Sergio San Juan Dertkigil; Andrei Sposito; Jose Roberto Matos-Souza; Thiago Quinaglia; Tomas G Neilan; Licio A Velloso; Wilson Nadruz; Michael Jerosch-Herold; Otavio R Coelho-Filho

doi:10.1016/j.heliyon.2024.e27206

Profile of serum microRNAs in heart failure with reduced and preserved ejection fraction: Correlation with myocardial remodeling

Heliyon. 2024 Mar 7;10(6):e27206. doi: 10.1016/j.heliyon.2024.e27206. eCollection 2024 Mar 30.

Authors

Layde Rosane Paim¹, Luis Miguel da Silva¹, Lígia M Antunes-Correa¹, Vinicius Citelli Ribeiro¹, Roberto Schreiber¹, Eduarda O Z Minin¹, Larissa C M Bueno¹, Elisangela C P Lopes¹, Renan Yamaguti², Andréa Coy-Canguçu³, Sergio San Juan Dertkigil¹, Andrei Sposito¹, Jose Roberto Matos-Souza¹, Thiago Quinaglia^{1

4}, Tomas G Neilan⁴, Licio A Velloso¹, Wilson Nadruz¹, Michael Jerosch-Herold⁵, Otavio R Coelho-Filho¹

Affiliations

¹ Faculdade de Ciências Médicas - Universidade Estadual de Campinas, São Paulo, Brazil.
² Faculdade de Engenharia Elétrica e de Computação - Universidade Estadual de Campinas, São Paulo, Brazil.
³ Faculdade de Medicina - Pontifícia Universidade Católica de Campinas, São Paulo, Brazil.
⁴ Cardiovascular Imaging Research Center, Division of Cardiology and Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁵ Non-Invasive Cardiovascular Imaging Program, Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Abstract

Background and aims: Cardiomyocyte hypertrophy and interstitial fibrosis are key components of myocardial remodeling in Heart Failure (HF) with preserved (HFpEF) or reduced ejection fraction (HFrEF). MicroRNAs (miRNAs) are non-coding, evolutionarily conserved RNA molecules that may offer novel insights into myocardial remodeling. This study aimed to characterize miRNA expression in HFpEF (LVEF $\geq$ 45%) and HFrEF (LVEF < 45%) and its association with myocardial remodeling.

Methods: Prospectively enrolled symptomatic HF patients (HFpEF:n = 36; HFrEF:n = 31) and controls (n = 23) underwent cardiac magnetic resonance imaging with T1-mapping and circulating miRNA expression (OpenArray system).

Results: 13 of 188 miRNAs were differentially expressed between HF groups (11 downregulated in HFpEF). Myocardial extracellular volume (ECV) was increased in both HF groups (HFpEF 30 ± 5%; HFrEF 30 ± 3%; controls 26 ± 2%, p < 0.001). miR-128a-3p, linked to cardiac hypertrophy, fibrosis, and dysfunction, correlated positively with ECV in HFpEF (r = 0.60, p = 0.01) and negatively in HFrEF (r = $-$ 0.51, p = 0.04). miR-423-5p overexpression, previously associated HF mortality, was inversely associated with LVEF (r = $-$ 0.29, p = 0.04) and intracellular water lifetime ( $τ$ _ic) (r = $-$ 0.45, p < 0.05) in both HF groups, and with NT-proBNP in HFpEF (r = $-$ 0.63, p < 0.01).

Conclusions: miRNA expression profiles differed between HF phenotypes. The differential expression and association of miR-128a-3p with ECV may reflect the distinct vascular, interstitial, and cellular etiologies of HF phenotypes.

Keywords: Biomarkers; Heart failure; Interstitial fibrosis; MicroRNA; Myocardial remodeling.