Rbm20 antisense oligonucleotides alleviate diastolic dysfunction in a mouse model of cardiometabolic heart failure (HFpEF).

ABSTRACT:

Aims

Heart failure with preserved ejection fraction (HFpEF) is prevalent, deadly, and difficult to treat. Risk factors such as obesity and hypertension contribute to cardiac inflammation, metabolic defects, and pathological remodelling that impair ventricular filling in diastole. Titin based stiffness is a main determinant of diastolic function and can be adjusted by the splicing regulator RNA binding motif protein 20 (RBM20). Inhibition of RBM20 using antisense oligonucleotides (ASOs) induces expression of compliant titin isoforms, which reduce stiffness. However, dose finding and documenting utility in primarily cardiometabolic disease remains challenging.

Methods and results

Here, we optimized RBM20-ASO dosing in a HFpEF mouse model that closely mimics human disease, char

SUBMITTER: Methawasin M 

PROVIDER: S-EPMC12560776 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature