“Young at heart”: Regenerative potential linked to immature cardiac phenotypes

Gomes, Renata S. M.; Skroblin, Philipp; Munster, Alex B.; Tomlins, Hannah; Langley, Sarah R.; Zampetaki, Anna; Yin, Xiaoke; Wardle, Fiona C.; Mayr, Manuel

doi:10.1016/j.yjmcc.2016.01.026

Cited by 21 publications

(15 citation statements)

References 15 publications

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“…The expression levels of cardiomyocyte-specific structural proteins exhibited an anticipated pattern with a switch from Myh7 to Myh6 and from Tnni1 to Tnni3 within the early postnatal period ( Figure 2C). 28,29 Also the expression profiles of the main cardiomyocyte ion channels (Supplemental Figure S3A) were in line with previous reports. 30 The expression patterns of control genes are presented in Supplemental Figure S3B.…”

Section: Transcriptomicssupporting

confidence: 90%

Molecular atlas of postnatal mouse heart development

Talman

Teppo

Pöhö

et al. 2018

Preprint

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Rationale: Mammals lose the ability to regenerate their hearts within one week after birth. During this regenerative window, cardiac energy metabolism shifts from glycolysis to fatty acid oxidation, and recent evidence suggests that metabolism may participate in controlling cardiomyocyte cell cycle. However, the molecular mechanisms mediating the loss of postnatal cardiac regeneration are not fully understood.Objective: This study aims at providing an integrated resource of mRNA, protein and metabolite changes in the neonatal heart to identify metabolism-related mechanisms associated with the postnatal loss of regenerative capacity. Methods and Results: Mouse ventricular tissue samples taken on postnatal days 1, 4, 9 and 23 (P01, P04, P09 and P23, respectively) were analyzed with RNA sequencing (RNAseq) and global proteomics and metabolomics. Differential expression was observed for 8547 mRNAs and for 1199 of the 2285 quantified proteins. Furthermore, 151 metabolites with significant changes were identified. Gene ontology analysis, KEGG pathway analysis and fuzzy c-means clustering were used to identify biological processes and metabolic pathways either up-or downregulated on all three levels. Among these were branched chain amino acid degradation (upregulated at P23) and production of free saturated and monounsaturated medium-to long-chain fatty acids (upregulated at P04 and P09; downregulated at P23). Moreover, the HMG-CoA synthase (HMGCS)-mediated mevalonate pathway and ketogenesis were transiently activated. Pharmacological inhibition of HMGCS in primary neonatal rat ventricular cardiomyocytes reduced the percentage of BrdU+ cardiomyocytes, providing evidence that the mevalonate and ketogenesis routes may participate in regulating cardiomyocyte cell cycle. Conclusions: This is the first systems-level resource combining data from genome-wide transcriptomics with global quantitative proteomics and untargeted metabolomics analyses of the mouse heart throughout the early postnatal period. This integrated multi-level data of molecular changes associated with the loss of cardiac regeneration may open up new possibilities for the development of regenerative therapies.

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Section: Transcriptomicssupporting

confidence: 90%

Molecular atlas of postnatal mouse heart development

Talman

Teppo

Pöhö

et al. 2018

Preprint

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“…Conserved SEPT7 expression was proved in both embryonic and adult zebrafish hearts reflecting to its role in the developmental immaturity of the zebrafish heart compared with mammals. In adult hearts SEPT7 expression could mainly be detected in the endothelium and not directly in the cardiomyocytes (Gomes et al 2016). The SEPT7 (cdc10) gene has been shown to be expressed at different levels in the longissimus muscle (LM) between low-marbled and high-marbled steer groups.…”

Section: Expression Of Septins In Muscle In Various Organismsmentioning

confidence: 99%

Septins, a cytoskeletal protein family, with emerging role in striated muscle

Gönczi

Dienes

Dobrosi

et al. 2020

J Muscle Res Cell Motil

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Appropriate organization of cytoskeletal components are required for normal distribution and intracellular localization of different ion channels and proteins involved in calcium homeostasis, signal transduction, and contractile function of striated muscle. Proteins of the contractile system are in direct or indirect connection with the extrasarcomeric cytoskeleton. A number of other molecules which have essential role in regulating stretch-, voltage-, and chemical signal transduction from the surface into the cytoplasm or other intracellular compartments are already well characterized. Sarcomere, the basic contractile unit, is comprised of a precisely organized system of thin (actin), and thick (myosin) filaments. Intermediate filaments connect the sarcomeres and other organelles (mitochondria and nucleus), and are responsible for the cellular integrity. Interacting proteins have a very diverse function in coupling of the intracellular assembly components and regulating the normal physiological function. Despite the more and more intense investigations of a new cytoskeletal protein family, the septins, only limited information is available regarding their expression and role in striated, especially in skeletal muscles. In this review we collected basic and specified knowledge regarding this protein group and emphasize the importance of this emerging field in skeletal muscle biology.

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“…Proteomic analyses comparing zebrafish hearts with neonatal and adult mouse hearts reveal striking differences in the myofilament composition. Interestingly, zebrafish hearts are similar to neonatal mouse hearts and are characterized by an immature myofilament composition that lacks many of the structural proteins present in mature adult cardiomyocytes 157 ( Figure 3 ). The plasticity of zebrafish and neonatal cardiomyocytes and their capacity to dedifferentiate can be linked to their immature sarcomere composition.…”

Section: Evolution and Ontogeny Of Cardiac Morphology And Physiologymentioning

confidence: 99%

Evolution, comparative biology and ontogeny of vertebrate heart regeneration

2016

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There are 64,000 living species of vertebrates on our planet and all of them have a heart. Comparative analyses devoted to understanding the regenerative potential of the myocardium have been performed in a dozen vertebrate species with the aim of developing regenerative therapies for human heart disease. Based on this relatively small selection of animal models, important insights into the evolutionary conservation of regenerative mechanisms have been gained. In this review, we survey cardiac regeneration studies in diverse species to provide an evolutionary context for the lack of regenerative capacity in the adult mammalian heart. Our analyses highlight the importance of cardiac adaptations that have occurred over hundreds of millions of years during the transition from aquatic to terrestrial life, as well as during the transition from the womb to an oxygen-rich environment at birth. We also discuss the evolution and ontogeny of cardiac morphological, physiological and metabolic adaptations in the context of heart regeneration. Taken together, our findings suggest that cardiac regenerative potential correlates with a low-metabolic state, the inability to regulate body temperature, low heart pressure, hypoxia, immature cardiomyocyte structure and an immature immune system. A more complete understanding of the evolutionary context and developmental mechanisms governing cardiac regenerative capacity would provide stronger scientific foundations for the translation of cardiac regeneration therapies into the clinic.

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“Young at heart”: Regenerative potential linked to immature cardiac phenotypes

Cited by 21 publications

References 15 publications

Molecular atlas of postnatal mouse heart development

Molecular atlas of postnatal mouse heart development

Septins, a cytoskeletal protein family, with emerging role in striated muscle

Evolution, comparative biology and ontogeny of vertebrate heart regeneration

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