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Murine neonatal cardiac regeneration depends on Insulin-like growth factor 1 receptor signaling
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Journal Article
Murine neonatal cardiac regeneration depends on Insulin-like growth factor 1 receptor signaling
2024
Overview
Unlike adult mammals, the hearts of neonatal mice possess the ability to completely regenerate from myocardial infarction (MI). This observation has sparked vast interest in deciphering the potentially lifesaving and morbidity-reducing mechanisms involved in neonatal cardiac regeneration. In mice, the regenerative potential is lost within the first week of life and coincides with a reduction of Insulin-like growth factor 1 receptor (
Igf1r
) expression in the heart.
Igf1r
is a well-known regulator of cardiomyocyte maturation and proliferation in neonatal mice. To test the role of
Igf1r
as a pivotal factor in cardiac regeneration, we knocked down (KD)
Igf1r
specifically in cardiomyocytes using recombinant adeno-associated virus (rAAV) delivery and troponin T promotor driven shRNAmirs. Cardiomyocyte specific
Igf1r
KD versus control mice were subjected to experimental MI by permanent ligation of the left anterior descending artery (LAD). Cardiac functional and morphological data were analyzed over a 21-day period. Neonatal
Igf1r
KD mice showed reduced systolic cardiac function and increased fibrotic cardiac remodeling 21 days post injury. This cardiac phenotype was associated with reduced cardiomyocyte nuclei mitosis and decreased AKT and ERK phosphorylation in
Igf1r
KD, compared to control neonatal mouse hearts. Our in vivo murine data show that
Igf1r
KD shifts neonatal cardiac regeneration to a more adult-like scarring phenotype, identifying cardiomyocyte-specific
Igf1r
signaling as a crucial component of neonatal cardiac regeneration.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ Animals
/ Heart
/ Humanities and Social Sciences
/ Insulin
/ Insulin-like growth factor 1 receptor
/ Mice
/ Mitosis
/ Myocardial Infarction - genetics
/ Myocardial Infarction - metabolism
/ Myocardial Infarction - pathology
/ Myocytes, Cardiac - metabolism
/ Neonatal cardiac regeneration
/ Neonates
/ Receptor, IGF Type 1 - genetics
/ Receptor, IGF Type 1 - metabolism
/ Science
/ Troponin
