Author:
Ruppert Mihály,Korkmaz-Icöz Sevil,Benczik Bettina,Ágg Bence,Nagy Dávid,Bálint Tímea,Sayour Alex Ali,Oláh Attila,Barta Bálint András,Benke Kálmán,Ferdinandy Péter,Karck Matthias,Merkely Béla,Radovits Tamás,Szabó Gábor
Abstract
AbstractAlthough 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 ABLVH). 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 ABHF). Global LV miRNA sequencing revealed fifty differentially regulated miRNAs in ABHF compared to ABLVH. 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 ABHF 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.
Funder
European Union
Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund
Hungarian Academy of Sciences
National Research, Development and Innovation Office (NKFIH) of Hungary
Ministry for Innovation and Technology from the National Research, Development and Innovation Fund source
National Research, Development and Innovation Office of Hungary
Semmelweis University
Publisher
Springer Science and Business Media LLC