Early sensitization of myofilaments to Ca2+ prevents genetically linked dilated cardiomyopathy in mice
نویسندگان
چکیده
منابع مشابه
X-linked dilated cardiomyopathy.
Background. X-linked cardiomyopathy (XLCM) is a rapidly progressive primary myocardial disorder presenting in teenage males as congestive heart failure. Manifesting female carriers have later onset (fifth decade) and slower progression. The purpose of this study was to localize the XLCM gene locus in two families using molecular genetic techniques. Methods and Results. Linkage analysis using 60...
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Dilated cardiomyopathy (DCM) is a devastating heart disease that affects about 1 million people in the United States, but the underlying mechanisms remain poorly understood. In this study, we aimed to determine the biomechanical and structural causes of DCM in transgenic mice carrying a novel mutation in the MYL2 gene, encoding the cardiac myosin regulatory light chain. Transgenic D94A (asparti...
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The sarcomere is the functional unit of the heart. Alterations in sarcomere activation lead to disease states such as hypertrophic and restrictive cardiomyopathy (HCM/RCM). Mutations in many of the sarcomeric genes are causal for HCM/RCM. In most cases, these mutations result in increased Ca(2+) sensitivity of the sarcomere, giving rise to altered systolic and diastolic function. There is emerg...
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The physiological consequences of aberrant Ca(2+) binding and exchange with cardiac myofilaments are not clearly understood. In order to examine the effect of decreasing Ca(2+) sensitivity of cTnC on cardiac function, we generated knock-in mice carrying a D73N mutation (not known to be associated with heart disease in human patients) in cTnC. The D73N mutation was engineered into the regulatory...
متن کاملMyofilament Ca2+ sensitization causes susceptibility to cardiac arrhythmia in mice.
In human cardiomyopathy, anatomical abnormalities such as hypertrophy and fibrosis contribute to the risk of ventricular arrhythmias and sudden death. Here we have shown that increased myofilament Ca2+ sensitivity, also a common feature in both inherited and acquired human cardiomyopathies, created arrhythmia susceptibility in mice, even in the absence of anatomical abnormalities. In mice expre...
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ژورنال
عنوان ژورنال: Cardiovascular Research
سال: 2017
ISSN: 0008-6363,1755-3245
DOI: 10.1093/cvr/cvx068