Publications by authors named "L W Carrier"

Sacubitril/valsartan (Sac/Val) belongs to the group of angiotensin receptor-neprilysin inhibitors and has been used for the treatment of heart failure (HF) for several years. The mechanisms that mediate the beneficial effects of Sac/Val are not yet fully understood. In this study we investigated whether Sac/Val influences the two proteolytic systems, the ubiquitin-proteasome system (UPS) and the autophagy-lysosomal pathway (ALP), in a mouse model of pressure overload induced by transverse aortic constriction (TAC) and in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) treated with endothelin-1 (ET1) serving as a human cellular model of hypertrophy.

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In the modern era, cardiologists managing patients and families with cardiomyopathies need to be familiar with every stage of the diagnostic pathway from clinical phenotyping to the prescription and interpretation of genetic tests. This clinical consensus statement from the ESC Council for Cardiovascular Genomics aims to promote the integration of genetic testing into routine cardiac care of patients with cardiomyopathies, as recommended in the 2023 ESC guidelines for cardiomyopathies. The document describes the types of genetic tests currently available and provides advice on their prescription and for counselling after the return of genetic findings, including the approach in patients and families with variants of unknown significance.

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Article Synopsis
  • * Advanced techniques such as adeno-associated viral vectors and CRISPR-Cas9 are proving to be efficient for gene delivery and repairing genetic issues in humans.
  • * The statement reviews various gene therapy approaches for heart failure and its causes, discusses their clinical applications, and highlights safety concerns and regulatory challenges for future development.
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Article Synopsis
  • - Hypertrophic cardiomyopathy (HCM) is a common genetic heart disorder linked to sarcomere gene mutations, resulting in left ventricular thickening and diastolic dysfunction; new research emphasizes the importance of microtubule alterations in heart failure.
  • - The study explored the effects of increasing tubulin tyrosination via adeno-associated virus transfer in various models, including HCM human cardiomyocytes and specific mouse models, revealing that this approach improved heart function by reducing harmful microtubule modifications and enhancing contractility.
  • - Results indicated that enhancing tubulin tyrosination led to better heart function metrics such as contractility and cardiac output in both human and mouse models, while also suggesting potential benefits of targeting the micro
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