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

TY - JOUR

T1 - Serial block face scanning electron microscopy reveals region dependent remodelling of transverse tubules post myocardial infarction

AU - Niort, Barbara

AU - Radcliffe, Emma

AU - Dibb, Katharine

A2 - Perera, Tharushi

A2 - Pius, Charlene

A2 - Trafford, Andrew

A2 - Pinali, Christian

N1 - Tharushi Perera is listed as external as she is not available on PURE, she did her MRes in the Division of Cardiovascular Sciences, University of Manchester and is currently an Manchester Medical School Yr 5 medical student. If you can add her to the UoM staff list then her affiliation from external to UoM can be corrected

PY - 2022/4/2

Y1 - 2022/4/2

N2 - 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.

AB - 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.

M3 - Article

JO - Royal Society of London. Philosophical Transactions B. Biological Sciences

JF - Royal Society of London. Philosophical Transactions B. Biological Sciences

SN - 0962-8436

M1 - RSTB-2021-0331.R1

ER -