Key result
Abdominal aortic banding-induced systolic heart failure in male rats is associated with unique miRNA alterations that negatively regulate the mRNA expression of Fmr1, Zfmp2, Wasl, Ets1, and Atg16l1 compared to hypertrophy without heart failure.
Why the study?
Although systolic function typically shows gradual impairment in pressure overload-induced LV hypertrophy, rapid progression to congestive heart failure occurs in distinct cases, with unknown underlying molecular mechanisms.
Pressure overload-evoked systolic heart failure is associated with unique miRNA alterations that negatively regulate specific mRNA expressions, providing potential novel molecular targets for heart failure.
miRNA changes in rat systolic HF are hypothesis-generating; leaves open their relevance as targets in human pressure-overload HF.
Although systolic function characteristically shows gradual impairment in pressure overload (PO)-evoked left ventricular (LV) hypertrophy (LVH), rapid progression to congestive heart failure (HF) occurs in distinct cases. The molecular mechanisms for the differences in maladaptation are unknown. Here, we examined microRNA (miRNA) expression and miRNA-driven posttranscriptional gene regulation in the two forms of PO-induced LVH (with/without systolic HF). PO was induced by aortic banding (AB) in male Sprague–Dawley rats. Sham-operated animals were controls. The majority of AB animals demonstrated concentric LVH and slightly decreased systolic function (termed as AB LVH ). In contrast, in some AB rats severely reduced ejection fraction, LV dilatation and increased lung weight-to-tibial length ratio was noted (referred to as AB HF ). Global LV miRNA sequencing revealed fifty differentially regulated miRNAs in AB HF compared to AB LVH . Network theoretical miRNA-target analysis predicted more than three thousand genes with miRNA-driven dysregulation between the two groups. Seventeen genes with high node strength value were selected for target validation, of which five ( Fmr1 , Zfpm2 , Wasl , Ets1, Atg16l1 ) showed decreased mRNA expression in AB HF by PCR. PO-evoked systolic HF is associated with unique miRNA alterations, which negatively regulate the mRNA expression of Fmr1 , Zfmp2 , Wasl , Ets1 and Atg16l1 .
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Ruppert et al. (2023) studied Pressure overload-induced systolic heart failure (n=63). Abdominal aortic banding vs. Sham operation and aortic banding without heart failure (ABLVH) was evaluated on Myocardial mRNA expression of Fmr1, Zfmp2, Wasl, Ets1 and Atg16l1 (p=<0.05). Abdominal aortic banding-induced systolic heart failure in male rats is associated with unique miRNA alterations that negatively regulate the mRNA expression of Fmr1, Zfmp2, Wasl, Ets1, and Atg16l1 compared to hypertrophy without heart failure.
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