A perspective on Notch signalling in progression and arrhythmogenesis in familial hypertrophic and dilated cardiomyopathies

In this perspective, we discussed emerging data indicating a role for Notch signalling in inherited disorders of the heart failure with focus on hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) linked to variants of genes encoding mutant proteins of the sarcomere. We recently reported an upregulation of elements in the Notch signalling cascade in cardiomyocytes derived from human inducible pluripotent stem cells expressing a TNNT2 variant encoding cardiac troponin T (cTnT-I79N+/-), which induces hypertrophy, remodelling, abnormalities in excitation-contraction coupling and electrical instabilities (Shafaattalab S et al. 2021 Front. Cell Dev. Biol. 9, 787581. (doi:10.3389/fcell.2021.787581)). Our search of the literature revealed the novelty of this finding and stimulated us to discuss potential connections between the Notch signalling pathway and familial cardiomyopathies. Our considerations focused on the potential role of these interactions in arrhythmias, microvascular ischaemia, and fibrosis. This finding underscored a need to consider the role of Notch signalling in familial cardiomyopathies which are trigged by sarcomere mutations engaging mechano-signalling pathways for which there is evidence of a role for Notch signalling with crosstalk with Hippo signalling. Our discussion included a role for both cardiac myocytes and non-cardiac myocytes in progression of HCM and DCM. This article is part of the theme issue 'The heartbeat: its molecular basis and physiological mechanisms'.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:378

Enthalten in:

Philosophical transactions of the Royal Society of London. Series B, Biological sciences - 378(2023), 1879 vom: 19. Juni, Seite 20220176

Sprache:

Englisch

Beteiligte Personen:

Langa, Paulina [VerfasserIn]
Shafaattalab, Sanam [VerfasserIn]
Goldspink, Paul H [VerfasserIn]
Wolska, Beata M [VerfasserIn]
Fernandes, Aurelia A [VerfasserIn]
Tibbits, Glen F [VerfasserIn]
Solaro, R John [VerfasserIn]

Links:

Volltext

Themen:

Arrythmias
Dilated cardiomyopathy
Hippo signalling
Hypertrophic cardiomyopathy
Journal Article
Notch
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Troponin T

Anmerkungen:

Date Completed 02.05.2023

Date Revised 03.05.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1098/rstb.2022.0176

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM356255905