Tissue Characterization

1357704 - Profiles of Serum MicroRNAs Differ Between Heart Failure with Reduced and Preserved Ejection Fraction and Correlate With Myocardial Remodeling

Wednesday, January 25, 2023

Location: E-POSTER

Presenting Author(s)

AC

Andréa Coy-Canguçu

BSc Student
Catholic Pontifical University of Campinas
Campinas, Sao Paulo, Brazil

Primary Author(s)

LP

Layde Paim

Post-Doctoral Student
State University of Campinas, Brazil

Co-Author(s)

LD

Luis Miguel Da Silva

Doctoral Student
State University of Campinas, Brazil
LA

Lígia Antunes-Correa

Assistant Professor
State University of Campinas, Brazil
VR

Vinicius Ribeiro

Researcher
State University of Campinas, Brazil
RS

Roberto Schreiber

Researcher
State University of Campinas, Brazil
EM

Eduarda Minin

Student
State University of Campinas, Brazil
LB

Larissa Bueno

Researcher
State University of Campinas, Brazil
EL

Elisangela Lopes

Researcher
State University of Campinas, Brazil
RY

Renan Yamaguti

BSc Student
State University of Campinas, Brazil
SD

Sergio Dertkigil

Researcher
State University of Campinas, Brazil
AS

Andrei Sposito

Full Professor
University of Campinas, Brazil
JM

José Roberto Mattos-Souza, MD, PhD

Researcher
State University of Campinas, Sao Paulo, Brazil
Tomas G. Neilan, MD

Director, Cardio-Oncology Program
Massachusetts General Hospital
Newton, Massachusetts, United States
WN

Wilson Nadruz, Jr., MD, PhD

Associate Professor
State University of Campinas, Sao Paulo, Brazil
MJ

Michael Jerosch-Herold, PhD

Associate Professor
Harvard Medical School, United States
Otavio Coelho-Filho, MD, PhD, MPH

Associate Professor
University of Campinas - UNICAMP
Campinas, Brazil

Background: Cardiomyocyte hypertrophy and increased 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 the determinants of myocardial remodeling in HF phenotypes and have been scantily correlated with myocardial tissue remodeling. We aimed to characterize miRNA expression profiles in HFpEF (LVEF≥45%) and HFrEF (LVEF < 45%) and their association with markers of myocardium remodeling.

Methods: Symptomatic HF patients (NYHA II-III) (HFpEF: n=36; HFrEF: n=31) and 23 healthy controls were prospectively enrolled and subjected to cardiac magnetic resonance (CMR) imaging. Circulating miRNA expression from blood serum samples analyses were conducted using the OpenArray system.

Results:

Of the 188 miRNAs found in both HF phenotypes, 13 were differentially expressed between HFpEF and HFrEF patients, with 11 of them downregulated in HFpEF (Fig 1). Although late gadolinium enhancement was more frequent in HFrEF (71.0%) than in HFpEF (47.1%, p=0.03), myocardial extracellular volume fraction (ECV) was similarly increased in both HF groups compared to controls (HFpEF 30±5%; HFrEF 30±3; controls 26±2, p< 0.001, Fig 2). While LV mass index was increased in both HF groups (HFpEF 68.7±25.7 g/m²; HFrEF 85.6±40.6; controls 41.8±8.1, p< 0.001), the intracellular water lifetime (τic), a marker of cardiomyocyte diameter, was elevated in HFpEF (HFpEF 0.15±0.05 s; HFrEF 0.11±0.04, p=0.01). Correlation analysis showed that miR-128-a-3p, which when upregulated has been linked to cardiac hypertrophy, fibrosis, and LV function impairment, correlated with ECV in both HF groups, but following distinct patterns (HFrEF R=-0.51, p=0.04; HFpEF R=0.60, p=0.01) (Fig 3). miR-423-5p overexpression, previously associated with increased mortality in HF, was inversely associated with LVEF (R=-0.29, p=0.04) and _ic(R=-0.45, p< 0.05) in both HF groups, and with NT-proBNP in the HFpEF group (τicR=-0.49, p=0.02; NT-proBNP R=-0.63, p=0.001). Both miRNAs were downregulated in HFpEF compared to HFrEF.

Conclusion:

MiRNA expression profiles differed significantly between HFpEF and HFrEF patients, indicating that: [1] the overexpression of miR-423-5p in the HFrEF group was associated with LV dysfunction, hypertrophy, and eccentric remodeling by greater τic and NT-proBNP values; and [2] underexpression of miR-128-a-3p in the HFpEF group was associated with diffuse myocardial fibrosis by increased ECV. The positive association between miR-128-a-3p and ECV among HFpEF patients indicates that this pathway plays a role in the progression of myocardial remodeling in this HF phenotype, in contrast to a negative association in HFrEF patients. The differential expression of miR-128-a-3p in HF subtypes and the differential association of miR-128-a-3p with ECV may reflect the distinct vascular, interstitial, and cellular etiologies of HFrEF and HFpEF.