Acute regional changes in myocardial strain may predict ventricular remodelling after myocardial infarction in a large animal model

DS  Mansell; Vito Domenico Bruno; Eva Sammut; A Chiribiri; Thomas W Johnson; Igor Khaliulin; Daniel Baz Lopez; HS Gill; KH Fraser; M Murphy; T Krieg; M-Saadeh Suleiman; Sarah J George; Raimondo Ascione; AN Cookson

doi:10.1038/s41598-021-97834-y

Acute regional changes in myocardial strain may predict ventricular remodelling after myocardial infarction in a large animal model

DS Mansell, Vito Domenico Bruno, Eva Sammut, A Chiribiri, Thomas W Johnson, Igor Khaliulin, Daniel Baz Lopez, HS Gill, KH Fraser, M Murphy, T Krieg, M-Saadeh Suleiman, Sarah J George, Raimondo Ascione^*, AN Cookson

^*Corresponding author for this work

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Abstract

To identify predictors of left ventricular remodelling (LVR) post-myocardial infarction (MI) and related molecular signatures, a porcine model of closed-chest balloon MI was used along with serial cardiac magnetic resonance imaging (CMRI) up to 5-6 weeks post-MI. Changes in myocardial strain and strain rates were derived from CMRI data. Tissue proteomics was compared between infarcted and non-infarcted territories. Peak values of left ventricular (LV) apical circumferential strain (ACS) changed over time together with peak global circumferential strain (GCS) while peak GLS epicardial strains or strain rates did not change over time. Early LVR post-MI enhanced abundance of 39 proteins in infarcted LV territories, 21 of which correlated with LV equatorial circumferential strain rate (ECSR). The strongest associations were observed for D-3-phosphoglycerate dehydrogenase (D-3PGDH), cysteine and glycine-rich protein-2 (CG-RP-2), and secreted frizzled-related protein 1 (sFRP1).
This study shows that early changes in regional peak ACS persist at 5-6 weeks post-MI, when early LVR is observed along with increased tissue levels of D-3PGDH and sFRP1. More studies are needed to ascertain if the observed increase in tissue levels of D-3PGDH and sFRP1 might be casually involved in the pathogenesis of adverse LV remodelling.

Original language	English
Article number	18322
Journal	Scientific Reports
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41598-021-97834-y
Publication status	Published - 15 Sep 2021

Bibliographical note

Funding Information:
This work was supported by a Great West 4 (GW4) Initiator grant to Ascione (GW4-AF4-011) and partially by the University of Bath. In addition, this work was supported by the following grants to Ascione: Medical Research Council (MRC): MR/L012723/1; British Heart Foundation (BHF): IG/14/2/30991, PG/10/40/28369, PG/07/046/22772, and PG/16/104/32652) to Ascione, and by a Developmental Pathway Funding Scheme (DPFS) grant to Murphy, Krieg and Ascione (MR/M015769/1). Mansell was supported by an EPSRC DTP.

Funding Information:
The authors would like to thank the staff at the University of Bristol Translational Biomedical Research Centre, a national research facility for large animal co-funded by the British Heart Foundation and the Medical Research Council.

Publisher Copyright:
© 2021, The Author(s).

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Mansell, DS., Bruno, V. D., Sammut, E., Chiribiri, A., Johnson, T. W., Khaliulin, I., Baz Lopez, D., Gill, HS., Fraser, KH., Murphy, M., Krieg, T., Suleiman, M-S., George, S. J., Ascione, R., & Cookson, AN. (2021). Acute regional changes in myocardial strain may predict ventricular remodelling after myocardial infarction in a large animal model. Scientific Reports, 11(1), [18322]. https://doi.org/10.1038/s41598-021-97834-y

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title = "Acute regional changes in myocardial strain may predict ventricular remodelling after myocardial infarction in a large animal model",

abstract = "To identify predictors of left ventricular remodelling (LVR) post-myocardial infarction (MI) and related molecular signatures, a porcine model of closed-chest balloon MI was used along with serial cardiac magnetic resonance imaging (CMRI) up to 5-6 weeks post-MI. Changes in myocardial strain and strain rates were derived from CMRI data. Tissue proteomics was compared between infarcted and non-infarcted territories. Peak values of left ventricular (LV) apical circumferential strain (ACS) changed over time together with peak global circumferential strain (GCS) while peak GLS epicardial strains or strain rates did not change over time. Early LVR post-MI enhanced abundance of 39 proteins in infarcted LV territories, 21 of which correlated with LV equatorial circumferential strain rate (ECSR). The strongest associations were observed for D-3-phosphoglycerate dehydrogenase (D-3PGDH), cysteine and glycine-rich protein-2 (CG-RP-2), and secreted frizzled-related protein 1 (sFRP1). This study shows that early changes in regional peak ACS persist at 5-6 weeks post-MI, when early LVR is observed along with increased tissue levels of D-3PGDH and sFRP1. More studies are needed to ascertain if the observed increase in tissue levels of D-3PGDH and sFRP1 might be casually involved in the pathogenesis of adverse LV remodelling.",

author = "DS Mansell and Bruno, {Vito Domenico} and Eva Sammut and A Chiribiri and Johnson, {Thomas W} and Igor Khaliulin and {Baz Lopez}, Daniel and HS Gill and KH Fraser and M Murphy and T Krieg and M-Saadeh Suleiman and George, {Sarah J} and Raimondo Ascione and AN Cookson",

note = "Funding Information: This work was supported by a Great West 4 (GW4) Initiator grant to Ascione (GW4-AF4-011) and partially by the University of Bath. In addition, this work was supported by the following grants to Ascione: Medical Research Council (MRC): MR/L012723/1; British Heart Foundation (BHF): IG/14/2/30991, PG/10/40/28369, PG/07/046/22772, and PG/16/104/32652) to Ascione, and by a Developmental Pathway Funding Scheme (DPFS) grant to Murphy, Krieg and Ascione (MR/M015769/1). Mansell was supported by an EPSRC DTP. Funding Information: The authors would like to thank the staff at the University of Bristol Translational Biomedical Research Centre, a national research facility for large animal co-funded by the British Heart Foundation and the Medical Research Council. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

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doi = "10.1038/s41598-021-97834-y",

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Mansell, DS, Bruno, VD, Sammut, E, Chiribiri, A, Johnson, TW , Khaliulin, I , Baz Lopez, D, Gill, HS, Fraser, KH, Murphy, M, Krieg, T, Suleiman, M-S , George, SJ , Ascione, R & Cookson, AN 2021, 'Acute regional changes in myocardial strain may predict ventricular remodelling after myocardial infarction in a large animal model', Scientific Reports, vol. 11, no. 1, 18322. https://doi.org/10.1038/s41598-021-97834-y

TY - JOUR

T1 - Acute regional changes in myocardial strain may predict ventricular remodelling after myocardial infarction in a large animal model

AU - Mansell, DS

AU - Bruno, Vito Domenico

AU - Sammut, Eva

AU - Chiribiri, A

AU - Johnson, Thomas W

AU - Khaliulin, Igor

AU - Baz Lopez, Daniel

AU - Gill, HS

AU - Fraser, KH

AU - Murphy, M

AU - Krieg, T

AU - Suleiman, M-Saadeh

AU - George, Sarah J

AU - Ascione, Raimondo

AU - Cookson, AN

N1 - Funding Information: This work was supported by a Great West 4 (GW4) Initiator grant to Ascione (GW4-AF4-011) and partially by the University of Bath. In addition, this work was supported by the following grants to Ascione: Medical Research Council (MRC): MR/L012723/1; British Heart Foundation (BHF): IG/14/2/30991, PG/10/40/28369, PG/07/046/22772, and PG/16/104/32652) to Ascione, and by a Developmental Pathway Funding Scheme (DPFS) grant to Murphy, Krieg and Ascione (MR/M015769/1). Mansell was supported by an EPSRC DTP. Funding Information: The authors would like to thank the staff at the University of Bristol Translational Biomedical Research Centre, a national research facility for large animal co-funded by the British Heart Foundation and the Medical Research Council. Publisher Copyright: © 2021, The Author(s).

PY - 2021/9/15

Y1 - 2021/9/15

N2 - To identify predictors of left ventricular remodelling (LVR) post-myocardial infarction (MI) and related molecular signatures, a porcine model of closed-chest balloon MI was used along with serial cardiac magnetic resonance imaging (CMRI) up to 5-6 weeks post-MI. Changes in myocardial strain and strain rates were derived from CMRI data. Tissue proteomics was compared between infarcted and non-infarcted territories. Peak values of left ventricular (LV) apical circumferential strain (ACS) changed over time together with peak global circumferential strain (GCS) while peak GLS epicardial strains or strain rates did not change over time. Early LVR post-MI enhanced abundance of 39 proteins in infarcted LV territories, 21 of which correlated with LV equatorial circumferential strain rate (ECSR). The strongest associations were observed for D-3-phosphoglycerate dehydrogenase (D-3PGDH), cysteine and glycine-rich protein-2 (CG-RP-2), and secreted frizzled-related protein 1 (sFRP1). This study shows that early changes in regional peak ACS persist at 5-6 weeks post-MI, when early LVR is observed along with increased tissue levels of D-3PGDH and sFRP1. More studies are needed to ascertain if the observed increase in tissue levels of D-3PGDH and sFRP1 might be casually involved in the pathogenesis of adverse LV remodelling.

AB - To identify predictors of left ventricular remodelling (LVR) post-myocardial infarction (MI) and related molecular signatures, a porcine model of closed-chest balloon MI was used along with serial cardiac magnetic resonance imaging (CMRI) up to 5-6 weeks post-MI. Changes in myocardial strain and strain rates were derived from CMRI data. Tissue proteomics was compared between infarcted and non-infarcted territories. Peak values of left ventricular (LV) apical circumferential strain (ACS) changed over time together with peak global circumferential strain (GCS) while peak GLS epicardial strains or strain rates did not change over time. Early LVR post-MI enhanced abundance of 39 proteins in infarcted LV territories, 21 of which correlated with LV equatorial circumferential strain rate (ECSR). The strongest associations were observed for D-3-phosphoglycerate dehydrogenase (D-3PGDH), cysteine and glycine-rich protein-2 (CG-RP-2), and secreted frizzled-related protein 1 (sFRP1). This study shows that early changes in regional peak ACS persist at 5-6 weeks post-MI, when early LVR is observed along with increased tissue levels of D-3PGDH and sFRP1. More studies are needed to ascertain if the observed increase in tissue levels of D-3PGDH and sFRP1 might be casually involved in the pathogenesis of adverse LV remodelling.

U2 - 10.1038/s41598-021-97834-y

DO - 10.1038/s41598-021-97834-y

M3 - Article (Academic Journal)

C2 - 34526592

VL - 11

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 18322

ER -

Acute regional changes in myocardial strain may predict ventricular remodelling after myocardial infarction in a large animal model

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