Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Pathogenic Mechanisms of Hypertrophic Cardiomyopathy Beyond Sarcomere Dysfunction

Version 1 : Received: 9 July 2021 / Approved: 12 July 2021 / Online: 12 July 2021 (12:13:53 CEST)

A peer-reviewed article of this Preprint also exists.

Chou, C.; Chin, M.T. Pathogenic Mechanisms of Hypertrophic Cardiomyopathy beyond Sarcomere Dysfunction. Int. J. Mol. Sci. 2021, 22, 8933. Chou, C.; Chin, M.T. Pathogenic Mechanisms of Hypertrophic Cardiomyopathy beyond Sarcomere Dysfunction. Int. J. Mol. Sci. 2021, 22, 8933.

Journal reference: Int. J. Mol. Sci. 2021, 22, 8933
DOI: 10.3390/ijms22168933

Abstract

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder affecting 1 in 500 people in the general population. Although characterized by asymmetric left ventricular hypertrophy, cardiomyocyte disarray and cardiac fibrosis, HCM is in fact a highly complex disease with heterogenous clinical presentation, onset and complications. While HCM is generally accepted as a disease of the sarcomere, variable penetrance in families with identical genetic mutations challenges the monogenic origin of HCM and instead implies a multifactorial cause. Furthermore, large scale genome sequencing studies revealed that many genes previously reported as causative of HCM in fact have little or no evidence of disease association. These findings thus call for a re-evaluation of the sarcomere-centered view of HCM pathogenesis. Here, we summarize our current understanding of sarcomere-independent mechanisms of cardiomyocyte hypertrophy, highlight the role of extracellular signals in cardiac fibrosis, and propose an alternative but integrated model of HCM pathogenesis.

Keywords

hypertrophic cardiomyopathy; pathological cardiac hypertrophy; sarcomere; cardiac myocyte; cardiac fibroblast; cardiac fibrosis; myocyte-fibroblast interaction; extracellular matrix

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