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- W4372337894 endingPage "100036" @default.
- W4372337894 startingPage "100036" @default.
- W4372337894 abstract "Hypertrophic cardiomyopathy (HCM) is a frequent inherited form of heart failure. The underlying cause of HCM is generally attributed to mutations in genes that encode for sarcomeric proteins, but the pathogenesis of the disease is also influenced by non-genetic factors, which can contribute to diastolic dysfunction and hypertrophic remodeling. Central to the pathogenesis of HCM is hypercontractility, a state that is an antecedent to several key derangements, including increased mitochondrial workload and oxidative stress. As a result, energy depletion and mechano-energetic uncoupling drive cardiac growth through signaling pathways such as ERK and/or potentially AMPK downregulation. Metabolic remodeling also occurs in HCM, characterized by decreased fatty acid oxidation and increased glucose uptake. In some instances, ketones may also feed the heart with energy and act as signaling molecules to reduce oxidative stress and hypertrophic signaling. In addition, arrhythmias are frequently triggered in HCM, resulting from the high Ca2+-buffering of the myofilaments and changes in the ATP/ADP ratio. Understanding the mechanisms driving the progression of HCM is critical to the development of effective therapeutic strategies. This paper presents evidence from both experimental and clinical studies that support the role of hypercontractility and cellular energy alterations in the progression of HCM towards heart failure and sudden cardiac death." @default.
- W4372337894 created "2023-05-07" @default.
- W4372337894 creator A5042728364 @default.
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- W4372337894 creator A5060960249 @default.
- W4372337894 creator A5067100967 @default.
- W4372337894 creator A5079194862 @default.
- W4372337894 date "2023-06-01" @default.
- W4372337894 modified "2023-09-26" @default.
- W4372337894 title "Mechano-energetic uncoupling in hypertrophic cardiomyopathy: Pathophysiological mechanisms and therapeutic opportunities" @default.
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