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Key Words: Ca 2ϩ /calmodulin-dependent protein kinase II Ⅲ sarcoplasmic reticulum Ca 2ϩ leak Ⅲ atrial fibrillation Ⅲ Ca 2ϩ sparks Ⅲ ryanodine receptor A trial fibrillation (AF) is the most frequent sustained arrhythmia in clinical practice. 1 In AF, both structural and electrophysiological remodeling of the atrial myocardium occurs, leading to increased(More)
Rationale: Heart failure (HF) is known to be associated with increased Ca 2؉ /calmodulin-dependent protein kinase (CaMK)II expression and activity. There is still controversial discussion about the functional role of CaMKII in HF. Moreover, CaMKII inhibition has never been investigated in human myocardium. Objective: We sought to investigate detailed(More)
BACKGROUND Transgenic (TG) Ca/calmodulin-dependent protein kinase II (CaMKII)delta(C) mice have heart failure and isoproterenol (ISO)-inducible arrhythmias. We hypothesized that CaMKII contributes to arrhythmias and underlying cellular events and that inhibition of CaMKII reduces cardiac arrhythmogenesis in vitro and in vivo. METHODS AND RESULTS Under(More)
A trial fibrillation (AF) is the most common sustained arrhythmia. AF produces lifestyle-limiting symptoms and increases the risk of stroke and death, 1 but current therapies have limited efficacy. The renin-angiotensin system is upreg-ulated in cardiovascular disease, and elevated angiotensin II (Ang II) favors AF. Ang II activates NADPH oxidase, leading(More)
RATIONALE Telethonin (also known as titin-cap or t-cap) is a 19-kDa Z-disk protein with a unique β-sheet structure, hypothesized to assemble in a palindromic way with the N-terminal portion of titin and to constitute a signalosome participating in the process of cardiomechanosensing. In addition, a variety of telethonin mutations are associated with the(More)
AIMS Melusin is a muscle-specific chaperone protein whose expression is required for a compensatory hypertrophy response to pressure overload. Here, we evaluated the consequences of melusin overexpression in the setting of myocardial infarction (MI) using a comprehensive multicentre approach. METHODS AND RESULTS Mice overexpressing melusin in the heart(More)
Cardiac atrophy as a consequence of mechanical unloading develops following exposure to microgravity or prolonged bed rest. It also plays a central role in the reverse remodelling induced by left ventricular unloading in patients with heart failure. Surprisingly, the intracellular Ca2+ transients which are pivotal to electromechanical coupling and to(More)
Inhibitor-1 (I-1) modulates protein phosphatase 1 (PP1) activity and thereby counteracts the phosphorylation by kinases. I-1 is downregulated and deactivated in failing hearts, but whether its role is beneficial or detrimental remains controversial, and opposing therapeutic strategies have been proposed. Overactivity of Ca2+/calmodulin-dependent protein(More)
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