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• W2922176301 startingPage "661" @default.
• W2922176301 abstract "The classic clinical definition of hypertrophic cardiomyopathy (HCM) as originally described by Teare is deceptively simple, left ventricular hypertrophy in the absence of any identifiable cause. Longitudinal studies, however, including a seminal study performed by Frank and Braunwald in 1968, clearly described the disorder much as we know it today, a complex, progressive, and highly variable cardiomyopathy affecting ~ 1/500 individuals worldwide. Subsequent genetic linkage studies in the early 1990s identified mutations in virtually all of the protein components of the cardiac sarcomere as the primary molecular cause of HCM. In addition, a substantial proportion of inherited dilated cardiomyopathy (DCM) has also been linked to sarcomeric protein mutations. Despite our deep understanding of the overall function of the sarcomere as the primary driver of cardiac contractility, the ability to use genotype in patient management remains elusive. A persistent challenge in the field from both the biophysical and clinical standpoints is how to rigorously link high-resolution protein dynamics and mechanics to the long-term cardiovascular remodeling process that characterizes these complex disorders. In this review, we will explore the depth of the problem from both the standpoint of a multi-subunit, highly conserved and dynamic machine to the resultant clinical and structural human phenotype with an emphasis on new, integrative approaches that can be widely applied to identify both novel disease mechanisms and new therapeutic targets for these primary biophysical disorders of the cardiac sarcomere." @default.
• W2922176301 created "2019-03-22" @default.
• W2922176301 creator A5002880771 @default.
• W2922176301 creator A5018423651 @default.
• W2922176301 creator A5072803970 @default.
• W2922176301 date "2019-03-08" @default.
• W2922176301 modified "2023-10-15" @default.
• W2922176301 title "Moving beyond simple answers to complex disorders in sarcomeric cardiomyopathies: the role of integrated systems" @default.
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