Abstract
The giant protein titin provides the elastic backbone of the myofilament and is extensively spliced to adapt the mechanical properties of the ventricle. The titin splice factor RBM20 determines not only the elastic but also the contractile properties of the cardiac ventricle. Animal models that replicate phenotypic features of heart failure with preserved ejection fraction (HFpEF), such as increased stiffness of the cardiac ventricle, respond to a 50% reduction in RBM20 levels with improved diastolic filling and improved cardiac function.
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