Reducing RBM20 activity improves diastolic dysfunction and cardiac atrophy

• DOI: 10.1007/s00109-016-1483-3
• Publication Date: 2016-11-26T08:32:55Z
• Authors: Florian Hinze; Christoph Dieterich; Michael H. Radke; Henk Granzier; Michael Gotthardt
• Keywords: Cardiac muscle; Obscurin; Diastolic heart failure; Concentric hypertrophy

Impaired diastolic filling is a main contributor to heart failure with preserved ejection fraction (HFpEF), syndrome increasing prevalence and no treatment. Both collagen the giant sarcomeric protein titin determine function. Since titin's elastic properties can be adjusted physiologically, we evaluated titin-based stiffness as therapeutic target. We RBM20-dependent cardiac isoform expression in N2B knockout mouse increased ventricular stiffness. A ~50 % reduction of RBM20 activity does not only maintain diastole but also ameliorates atrophy thus improves function N2B-deficient heart. Reduced partially normalized gene related muscle development fatty acid metabolism. The adaptation growth was hypertrophy signaling via four-and-a-half lim-domain proteins (FHLs) that translate mechanical input into signals. provide novel link between trophic FHLs suggest splicing target dysfunction.