Differential response to injury in fetal and adolescent sheep hearts in the immediate post in the immediate post-myocardial myocardial myocardial infarction period

Mitchell C. Lock, Jack R.T. Darby, Jia Yin Soo, Doug A. Brooks, Raj Perumal, Joseph Selvanayagam, Mike Seed, Christopher K. MacGowan, Enzo R. Porrello, Ross L. Tellam, Janna L. Morrison

Research output: Contribution to journalArticle

Abstract

Aim: Characterizing the response to myocardial infarction (MI) in the regenerative sheep fetus heart compared to the post-natal non-regenerative adolescent heart may reveal key morphological and molecular differences that equate to the response to MI in humans. We hypothesized that the immediate response to injury in (a) infarct compared with sham, and (b) infarct, border, and remote tissue, in the fetal sheep heart would be fundamentally different to the adolescent, allowing for repair after damage. Methods: We used a sheep model of MI induced by ligating the left anterior descending coronary artery. Surgery was performed on fetuses (105 days) and adolescent sheep (6 months). Sheep were randomly separated into MI (n = 5) or Sham (n = 5) surgery groups at both ages. We used magnetic resonance imaging (MRI), histological/immunohistochemical staining, and qRT-PCR to assess the morphological and molecular differences between the different age groups in response to infarction. Results: Magnetic resonance imaging showed no difference in fetuses for key functional parameters; however there was a significant decrease in left ventricular ejection fraction and cardiac output in the adolescent sheep heart at 3 days post-infarction. There was no significant difference in functional parameters between MRI sessions at Day 0 and Day 3 after surgery. Expression of genes involved in glucose transport and fatty acid metabolism, inflammatory cytokines as well as growth factors and cell cycle regulators remained largely unchanged in the infarcted compared to sham ventricular tissue in the fetus, but were significantly dysregulated in the adolescent sheep. Different cardiac tissue region-specific gene expression profiles were observed between the fetal and adolescent sheep. Conclusion: Fetuses demonstrated a resistance to cardiac damage not observed in the adolescent animals. The manipulation of specific gene expression profiles to a fetal-like state may provide a therapeutic strategy to treat patients following an infarction.

LanguageEnglish
Article number208
JournalFrontiers in Physiology
Volume10
Issue numberMAR
DOIs
Publication statusPublished - 1 Mar 2019

Keywords

  • Cardiac
  • Fetus
  • Myocardial infarction
  • Proliferation
  • Repair
  • Sheep

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Lock, Mitchell C. ; Darby, Jack R.T. ; Soo, Jia Yin ; Brooks, Doug A. ; Perumal, Raj ; Selvanayagam, Joseph ; Seed, Mike ; MacGowan, Christopher K. ; Porrello, Enzo R. ; Tellam, Ross L. ; Morrison, Janna L. / Differential response to injury in fetal and adolescent sheep hearts in the immediate post in the immediate post-myocardial myocardial myocardial infarction period. In: Frontiers in Physiology. 2019 ; Vol. 10, No. MAR.
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Differential response to injury in fetal and adolescent sheep hearts in the immediate post in the immediate post-myocardial myocardial myocardial infarction period. / Lock, Mitchell C.; Darby, Jack R.T.; Soo, Jia Yin; Brooks, Doug A.; Perumal, Raj; Selvanayagam, Joseph; Seed, Mike; MacGowan, Christopher K.; Porrello, Enzo R.; Tellam, Ross L.; Morrison, Janna L.

In: Frontiers in Physiology, Vol. 10, No. MAR, 208, 01.03.2019.

Research output: Contribution to journalArticle

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T1 - Differential response to injury in fetal and adolescent sheep hearts in the immediate post in the immediate post-myocardial myocardial myocardial infarction period

AU - Lock, Mitchell C.

AU - Darby, Jack R.T.

AU - Soo, Jia Yin

AU - Brooks, Doug A.

AU - Perumal, Raj

AU - Selvanayagam, Joseph

AU - Seed, Mike

AU - MacGowan, Christopher K.

AU - Porrello, Enzo R.

AU - Tellam, Ross L.

AU - Morrison, Janna L.

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KW - Cardiac

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KW - Myocardial infarction

KW - Proliferation

KW - Repair

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