Early Postnatal Cardiomyocyte Proliferation Requires High Oxidative Energy Metabolism

Author(s)

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]

Affiliation

^[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

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 7, NOV 13 2017.
• Web of Science Citations: 6

Abstract

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)

• FAPESP's process: 12/10109-7 - Mitochondrial energy metabolism and cardiomyogenesis for cardiac regeneration
• Grantee: Ana Elisa Teófilo Saturi de Carvalho
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/17368-0 - Cardiovascular genomics: mechanisms & novel therapeutics - CVGen mech2ther
• Grantee: José Eduardo Krieger
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/04871-6 - Effects of caloric restriction on mitochondrial morphology, dynamics, bioenergetics and redox state
• Grantee: Maria Fernanda Pereira de Araújo Demonte Forni
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/26440-7 - Identification of surface markers in cardiac precursors of rats
• Grantee: Aline Alfonso Keusseyan
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 11/19678-1 - Cardiac progenitor cells identification and isolation using aptamers
• Grantee: Vinícius Bassaneze
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/25776-7 - Mitochondrial Partitioning in Mammalian Cells.
• Grantee: Maria Fernanda Pereira de Araújo Demonte Forni
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC