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

Research output: Contribution to journalArticlepeer-review

  • External authors:
  • Tharushi Perera (Lead)
  • Charlene Pius (Lead)
  • Barbara Niort
  • Emma Radcliffe

Abstract

The highly organised 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 organisation 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-myocardial infarction 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 (IR) MI model and matched controls.
We performed minimally invasive coronary angioplasty of the left anterior descending (LAD) artery, followed by reperfusion after 90 minutes to establish the MI model. Left ventricular tissues obtained from control and MI hearts 8-weeks post-MI were imaged using SBF-SEM. Image analysis generated 3-dimensional reconstructions of the t-tubular network in control, MI border and remote regions. Quantitative analysis revealed that the MI border region was characterised 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 localised therapeutic targets aimed at preservation or restoration of the t-tubules to manage cardiac contractility post-MI.

Bibliographical metadata

Original languageEnglish
Article numberRSTB-2021-0331.R1
JournalRoyal Society of London. Philosophical Transactions B. Biological Sciences
Publication statusAccepted/In press - 2 Apr 2022