Serial block face scanning electron microscopy reveals region-dependent remodelling of transverse tubules post-myocardial infarction.


Journal

Philosophical transactions of the Royal Society of London. Series B, Biological sciences
ISSN: 1471-2970
Titre abrégé: Philos Trans R Soc Lond B Biol Sci
Pays: England
ID NLM: 7503623

Informations de publication

Date de publication:
21 11 2022
Historique:
entrez: 3 10 2022
pubmed: 4 10 2022
medline: 5 10 2022
Statut: ppublish

Résumé

The highly organized transverse tubule (t-tubule) network facilitates cardiac excitation-contraction coupling and synchronous cardiac myocyte contraction. In cardiac failure secondary to myocardial infarction (MI), changes in the structure and organization of t-tubules result in impaired cardiac contractility. However, there is still little knowledge on the regional variation of t-tubule remodelling in cardiac failure post-MI. Here, we investigate post-MI t-tubule remodelling in infarct border and remote regions, using serial block face scanning electron microscopy (SBF-SEM) applied to a translationally relevant sheep ischaemia reperfusion MI model and matched controls. We performed minimally invasive coronary angioplasty of the left anterior descending artery, followed by reperfusion after 90 min to establish the MI model. Left ventricular tissues obtained from control and MI hearts eight weeks post-MI were imaged using SBF-SEM. Image analysis generated three-dimensional reconstructions of the t-tubular network in control, MI border and remote regions. Quantitative analysis revealed that the MI border region was characterized by t-tubule depletion and fragmentation, dilation of surviving t-tubules and t-tubule elongation. This study highlights region-dependent remodelling of the tubular network post-MI and may provide novel localized therapeutic targets aimed at preservation or restoration of the t-tubules to manage cardiac contractility post-MI. This article is part of the theme issue 'The cardiomyocyte: new revelations on the interplay between architecture and function in growth, health, and disease'.

Identifiants

pubmed: 36189812
doi: 10.1098/rstb.2021.0331
pmc: PMC9527908
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

20210331

Subventions

Organisme : British Heart Foundation
ID : PG/18/24/33608
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/18/4/33310
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/20/6/34990
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K5002823/1
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/17/52/33113
Pays : United Kingdom

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Auteurs

Tharushi Perera (T)

Unit of Cardiac Physiology, Division of Cardiovascular Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester Academic Health Sciences Centre, 46 Grafton Street, Manchester M13 9NT, UK.

Charlene Pius (C)

Unit of Cardiac Physiology, Division of Cardiovascular Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester Academic Health Sciences Centre, 46 Grafton Street, Manchester M13 9NT, UK.

Barbara Niort (B)

Unit of Cardiac Physiology, Division of Cardiovascular Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester Academic Health Sciences Centre, 46 Grafton Street, Manchester M13 9NT, UK.

Emma J Radcliffe (EJ)

Unit of Cardiac Physiology, Division of Cardiovascular Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester Academic Health Sciences Centre, 46 Grafton Street, Manchester M13 9NT, UK.

Katharine M Dibb (KM)

Unit of Cardiac Physiology, Division of Cardiovascular Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester Academic Health Sciences Centre, 46 Grafton Street, Manchester M13 9NT, UK.

Andrew W Trafford (AW)

Unit of Cardiac Physiology, Division of Cardiovascular Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester Academic Health Sciences Centre, 46 Grafton Street, Manchester M13 9NT, UK.

Christian Pinali (C)

Unit of Cardiac Physiology, Division of Cardiovascular Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester Academic Health Sciences Centre, 46 Grafton Street, Manchester M13 9NT, UK.

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