Early Postnatal Cardiomyocyte Proliferation Requires High Oxidative Energy Metabolism

Cardiac energy metabolism must cope with early postnatal changes in tissue oxygen tensions, hemodynamics, and cell proliferation to sustain development. Here, we tested the hypothesis that proliferating neonatal cardiomyocytes are dependent on high oxidative energy metabolism. We show that energy-re...

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Bibliographic Details
Published in:	Scientific reports Vol. 7; no. 1; pp. 15434 - 11
Main Authors:	de Carvalho, Ana Elisa Teófilo Saturi, Bassaneze, Vinícius, Forni, Maria Fernanda, Keusseyan, Aline Alfonso, Kowaltowski, Alicia Juliana, Krieger, José Eduardo
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 13-11-2017 Nature Publishing Group
Subjects:	13/106 14/1 14/19 38/91 631/443/592/2725 692/4019/592/2725 Animals Animals, Newborn Birth Cardiomyocytes Cell proliferation Cell Proliferation - physiology Cells, Cultured Electron transport Energy demand Energy metabolism Energy Metabolism - physiology Gene expression Glycolysis Glycolysis - physiology Heart Heart - growth & development Heart diseases Hemodynamics Humanities and Social Sciences Metabolism Mitochondria Mitochondria - chemistry Mitochondria - metabolism multidisciplinary Myocytes, Cardiac - cytology Myocytes, Cardiac - metabolism Neonates Oxidation-Reduction Oxidative metabolism Oxidative Stress - physiology Oxygen - analysis Oxygen - metabolism Primary Cell Culture Rats Rats, Wistar Respiration Science Science (multidisciplinary)
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Summary:	Cardiac energy metabolism must cope with early postnatal changes in tissue oxygen tensions, hemodynamics, and cell proliferation to sustain development. Here, we tested the hypothesis that proliferating neonatal cardiomyocytes are dependent on high oxidative energy metabolism. We show that energy-related gene expression does not correlate with functional oxidative measurements in the developing heart. Gene expression analysis suggests a gradual overall upregulation of oxidative-related genes and pathways, whereas functional assessment in both cardiac tissue and cultured cardiomyocytes indicated that oxidative metabolism decreases between the first and seventh days after birth. Cardiomyocyte extracellular flux analysis indicated that the decrease in oxidative metabolism between the first and seventh days after birth was mostly related to lower rates of ATP-linked mitochondrial respiration, suggesting that overall energetic demands decrease during this period. In parallel, the proliferation rate was higher for early cardiomyocytes. Furthermore, in vitro nonlethal chemical inhibition of mitochondrial respiration reduced the proliferative capacity of early cardiomyocytes, indicating a high energy demand to sustain cardiomyocyte proliferation. Altogether, we provide evidence that early postnatal cardiomyocyte proliferative capacity correlates with high oxidative energy metabolism. The energy requirement decreases as the proliferation ceases in the following days, and both oxidative-dependent metabolism and anaerobic glycolysis subside.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2045-2322 2045-2322
DOI:	10.1038/s41598-017-15656-3