T-tubule remodeling in human hypertrophic cardiomyopathy

Year: 2020

Authors: Vitale Giulia; Coppini Raffaele; Tesi Chiara; Poggesi Corrado; Sacconi Leonardo; Ferrantini Cecilia

Autors Affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; European Laboratory for Nonlinear Spectroscopy (LENS), University of Florence, Sesto Fiorentino, Italy; Department NeuroFarBa, University of Florence, Florence, Italy; National Institute of Optics, National Research Council,Florence, Italy

Abstract: The highly organized transverse T-tubule membrane system represents the ultrastructural substrate for excitation-contraction coupling in ventricular myocytes. While the architecture and function of T-tubules have been well described in animal models, there is limited morpho-functional data on T-tubules in human myocardium. Hypertrophic cardiomyopathy (HCM) is a primary disease of the heart muscle, characterized by different clinical presentations at the various stages of its progression. Most HCM patients, indeed, show a compensated hypertrophic disease (“non-failing hypertrophic phase”), with preserved left ventricular function, and only a small subset of individuals evolves into heart failure (“end stage HCM”). In terms of T-tubule remodeling, the “end-stage” disease does not differ from other forms of heart failure. In this review we aim to recapitulate the main structural features of T-tubules during the “non-failing hypertrophic stage” of human HCM by revisiting data obtained from human myectomy samples. Moreover, by comparing pathological changes observed in myectomy samples with those introduced by acute (experimentally induced) detubulation, we discuss the role of T-tubular disruption as a part of the complex excitation-contraction coupling remodeling process that occurs during disease progression. Lastly, we highlight how T-tubule morpho-functional changes may be related to patient genotype and we discuss the possibility of a primitive remodeling of the T-tubule system in rare HCM forms associated with genes coding for proteins implicated in T-tubule structural integrity, formation and maintenance.

Journal/Review: JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY

Volume: 42 (2)      Pages from: 305  to: 322

More Information: Open access funding provided by Universita degli Studi di Firenze within the CRUI-CARE Agreement. This research was supported by the European Union´s Horizon 2020 research and innovation programme, project SILICOFCM Grant Agreement No. 777204 and by Telethon-UILDM Grant Agreement No. GUP19012.
KeyWords: Excitation-contraction coupling, Hypertrophic cardiomyopathy, T-tubules
DOI: 10.1007/s10974-020-09591-6

Citations: 4
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