Alternative Splicing of Titin Restores Diastolic Function in an HFpEF-Like Genetic Murine Model (TtnΔIAjxn).

Alternative Splicing of Titin Restores Diastolic Function in an HFpEF-Like Genetic Murine Model (TtnΔIAjxn)

Myocardial titin and collagen in cardiac diastolic dysfunction: partners in crime.

H igh myocardial diastolic stiffness has usually been attributed to excessive myocardial collagen deposition. Over the last decennium, stiff cardiomyocytes were also identified as important contributors to high myocardial diastolic stiffness , especially in heart failure (HF) with preserved ejection fraction (HFPEF). Cardiomyocyte stiffness relates to elasticity of the giant cytoskeletal protei...

Deranged myofilament phosphorylation and function in experimental heart failure with preserved ejection fraction.

AIMS Heart failure (HF) with preserved ejection fraction (HFpEF) is a major cause of morbidity and mortality. Key alterations in HFpEF include increased left ventricular (LV) stiffness and abnormal relaxation. We hypothesized that myofilament protein phosphorylation and function are deranged in experimental HFpEF vs. normal myocardium. Such alterations may involve the giant elastic protein titi...

Cellular Biology Hyperphosphorylation of Mouse Cardiac Titin Contributes to Transverse Aortic Constriction-Induced Diastolic Dysfunction

Rationale: Mechanisms underlying diastolic dysfunction need to be better understood. Objective: To study the role of titin in diastolic dysfunction using a mouse model of experimental heart failure induced by transverse aortic constriction. titin-based passive stiffness. Changes in titin splicing occur, which lower passive stiffness, but this effect is offset by hyperphosphorylation of residues...

Myocardial stiffness in patients with heart failure and a preserved ejection fraction: contributions of collagen and titin.

BACKGROUND The purpose of this study was to determine whether patients with heart failure and a preserved ejection fraction (HFpEF) have an increase in passive myocardial stiffness and the extent to which discovered changes depend on changes in extracellular matrix fibrillar collagen and cardiomyocyte titin. METHODS AND RESULTS Seventy patients undergoing coronary artery bypass grafting under...