Serum expression of mirnas in obese and lean patients with heart failure
Authors: Schreiber R , Minin E O Z , Paim L R , Silva L M , Antunes-Correa L , Coy-Cangucu A , Dertkigil S S J , Sposito A , Matos-Souza J R , Neilan T G , Velloso L A , Nadruz W , Jerosch-Herold M , Coelho-Filho O R 
Published: October 2024

Abstract

Background
Heart Failure (HF) is a progressive disease that results in increased morbidity and mortality, and clinical studies have demonstrated that body mass index (BMI) is an independent risk factor for the development of HF. Evidence has suggested that human obesity is associated with reduced mortality among patients with HF, a clinical phenomenon known as the "Obesity Paradox." MicroRNAs (miRNAs) have been underscored for their pivotal regulatory roles in numerous diseases, particularly in the context of HF. Nevertheless, our understanding of the impact of these miRNAs on obesity in conjunction with HF remains limited.

Purpose
The objective of this study was to evaluate the serum expression of miRNAs in obese and lean patients with HF and establish the relationship between these miRNAs and BMI. Additionally, we explored this association within two distinct phenotypes: HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF).

Methods
Sixty-five patients with symptomatic HF (all NYHA &gt;/=II, mean-LVFE 44.4 %), 29 lean (BMI= 25.87 ± 2.52 Kg/m2) and 36 obese (BMI= 34.52 ± 4.15 Kg/m2), were prospectively evaluated by clinical, laboratory and echocardiographic analyses. Serum expression of miRNAs was assessed by the TaqMan OpenArray Human MicroRNA system, a polymerase chain reaction-based quantitative platform that contains 754 microRNAs in a microfluidic platform.

Results
Among the studied miRNAs, seventeen were upregulated and one downregulated in obese HF patients compared to lean HF patients (Figure 1A). Ten miRNAs were differentially expressed in the serum of obese HFpEF patients compared to lean HFrEF patients (Figure 1B) and five were differentially expressed in the serum of obese HFpEF patients when compared to lean HFpEF patients (Figure 1C). miR-132 was upregulated in obese patients with HFrEF and HFpEF compared to lean patients, whereas miR-1291 was downregulated only in obese patients with HFpEF. Correlation analysis demonstrated a positive association between BMI and miR-132 (r=0.502; p=0.001), miR-148b (r=0.510; p&lt;0.001), miR-103a-3p (r=0.373; p =0.011) and miR-374b-5p (r=0.325; p=0.034) in HF patients and gene set enrichment analysis identified seventy-nine potential target genes common to at least three of these four miRNAs, with the EIF4E3 and TRA2B genes common to the four miRNAs.

Conclusions
Our study reveals a profile of miRNAs that are differentially expressed in obese patients with HF when compared to lean patients with HF. Furthermore, four of these miRNAs showed a positive correlation with BMI in patients with HF. Although the literature indicates that miR-132 presents reduced expression in obesity models, our study identified increased serum expression of this miRNA, suggesting that it might be a potential "missing link" in the obesity paradox in patients with HF. Further studies with a larger sample are needed to confirm and explore the mechanisms linking these miRNAs to the obesity paradox.