Early Postnatal Cardiomyocyte Proliferation Requires High Oxidative Energy Metabolism

Autor(es)

Teofilo Saturi de Carvalho, Ana Elisa ^[1] ; Bassaneze, Vinicius ^[1] ; Forni, Maria Fernanda ^[2] ; Keusseyan, Aline Alfonso ^[1] ; Kowaltowski, Alicia Juliana ^[2] ; Krieger, Jose Eduardo ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Med Sch, Lab Genet & Mol Cardiol LIM 13, Heart Inst, InCor HCFMUSP, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Quim, Dept Bioquim, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 7, NOV 13 2017.
• Citações Web of Science: 6

Resumo

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. (AU)

• Processo FAPESP: 12/10109-7 - Metabolismo energético mitocondrial e cardiomiogênese para regeneração cardíaca
• Beneficiário: Ana Elisa Teófilo Saturi de Carvalho
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 13/17368-0 - Genômica cardiovascular: mechanismos & novas terapias - CVGen mech2ther
• Beneficiário: José Eduardo Krieger
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 13/04871-6 - Efeitos da restrição calórica sobre a morfologia, dinâmica, bioenergética e estado redox mitocondriais
• Beneficiário: Maria Fernanda Pereira de Araújo Demonte Forni
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/26440-7 - Identificação de marcadores de superfície de precursores cardíacos de ratos
• Beneficiário: Aline Alfonso Keusseyan
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 11/19678-1 - Identificação e isolamento de células progenitoras cardíacas usando aptâmeros
• Beneficiário: Vinícius Bassaneze
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/25776-7 - Mecanismos Moleculares do Particionamento Mitocondrial em Células de Mamífero.
• Beneficiário: Maria Fernanda Pereira de Araújo Demonte Forni
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/07937-8 - Redoxoma
• Beneficiário: Ohara Augusto
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs