Abstract
We evaluated the metabolic profile in pig hearts at postnatal day 1, 3, 7, and 28 (P1, P3, P7, and P28, respectively) using a targeted liquid chromatography tandem mass spectrometry assay. Our data showed that there is a clear separation of the detected metabolites in P1 vs. P28 hearts. Active anabolisms of nucleotide and proteins were observed in P1 hearts when cardiomyocytes retain high cell cycle activity. However, the active posttranslational protein modification, metabolic switch from glucose to fatty acids, and the reduced ratio of collagen to total protein were observed in P28 hearts when cardiomyocytes withdraw from cell cycle.
Highlights
Cardiomyocytes in adult mammals possess very limited regenerative potential as a result of cell cycle exit
A comparison between Postnatal day 1 (P1) and P7 hearts revealed a clear separation of metabolomic profiles (Figure 1F), and 25 metabolites were identified with differential expression (Figure 1G)
A comparison between P1 and P28 hearts revealed a clear separation of metabolomic profiles (Figure 1H), a total of 135 metabolites were detected and 74 metabolites were identified with differential expression
Summary
Cardiomyocytes in adult mammals possess very limited regenerative potential as a result of cell cycle exit. Myocardium loss after injuries is typically replaced by fibrotic scar. Several lines of evidence have shown that cardiomyocytes in neonatal mice [1] and pigs [2] retain regenerative capacity. We have recently shown that hearts of postnatal day 1 and day 2 pigs can regenerate lost myocardium in response to injury [2]. This regeneration is mediated by proliferation of preexisting cardiomyocytes, which does not occur when cardiomyocytes permanently exit cell cycle. Mechanisms underlying injury-mounted regenerative response especially in large mammals have not been fully understood
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