PhD Scientific Days 2022

Translational Medicine II. (Poster discussion will take place in the Aula during the Coffee Break)

The decompensation of systolic function in pressure overload-induced left ventricular myocardial hypertrophy is associated with unique microRNA expression profile

Text of the abstract

Introduction: microRNA (miRNA) expression is dysregulated in pressure overload (PO)-induced left ventricular (LV) myocardial hypertrophy (LVH). Nevertheless, whether the altered miRNA expression might contribute to the decompensation of LV systolic function is debated.
Aims: Hence, we aimed to characterize miRNA expression in PO-induced LVH with and without systolic heart failure (HF).
Methods: Aortic banding (AB) was performed in male rats to evoke PO. Sham-operated animals served as controls. Functional and morphological alterations were assessed by echocardiography and histology. At the end of the experimental period, rats in the AB group were subcategorized based on ejection fraction [EF] into ABLVH (EF>40%) and ABHF groups (EF<40%). Global miRNA expression profiling was performed using next generation sequencing. Bioinformatics analysis was carried out to predict miRNA-target interactions. Expression of selected target genes was measured by qRT-PCR.
Results: Increased heart weight-to-tibial length, LV mass and fibrosis confirmed the development of pathological LVH in both the ABLVH and ABHF groups. Nevertheless, increased lung weight-to-tibial length, chamber dilatation and severely reduced EF was noted only in the ABHF and not in the ABLVH, when compared to the sham group. 50 miRNA showed different expression in the ABHF compared to the ABLVH group. Based on the altered gene expression profile, in silico bioinformatics analysis predicted several target genes. Among them, reduced mRNA expression level of Fmr1 (FMRP translational regulator 1), Zfpm2 (zinc finger protein, multitype 2), Wasl (WASP like actin nucleation promoting factor), Ets1 (ETS proto-oncogene 1) and Atg16l1 (Autophagy Related 16 Like 1) was confirmed in ABHF compared to ABLVH.
Conclusions: Decompensation of systolic function in PO-induced LVH is associated with unique miRNA profile leading to specific regulation of gene expression.
Funding: New National Excellence Program of the Ministry of Human Capacities (ÚNKP-21-4-II-SE-5 to M.R.)