Does cardiac development provide heart research with novel therapeutic approaches?

Abstract

Embryonic heart progenitors arise at specific spatiotemporal periods that contribute to the formation of distinct cardiac structures. In mammals, the embryonic and fetal heart is hypoxic by comparison to the adult heart. In parallel, the cellular metabolism of the cardiac tissue, including progenitors, undergoes a glycolytic to oxidative switch that contributes to cardiac maturation. While oxidative metabolism is energy efficient, the glycolytic-hypoxic state may serve to maintain cardiac progenitor potential. Consistent with this proposal, the adult epicardium has been shown to contain a reservoir of quiescent cardiac progenitors that are activated in response to heart injury and are hypoxic by comparison to adjacent cardiac tissues. In this review, we discuss the development and potential of the adult epicardium and how this knowledge may provide future therapeutic approaches for cardiac repair.

Hypoxia promotes a perinatal-like progenitor state in the adult murine epicardium

“…There is considerable research effort aimed at identifying factors that activate the adult epicardium in order to promote a beneficial recovery following cardiac injury 43 , 68 , 77 – 83 . The embryonic and fetal hearts are physiologically hypoxic due to an underdeveloped cardiac vascular system and placenta restriction 12 , 25 – 28 , 49 , 50 , 84 , 85 , whereas the hypoxic state is only maintained in the adult mammalian epicardium, as shown in this study and by others 31 . The epicardium has been shown to drive heart morphogenesis and serve as a reservoir of progenitors of non-cardiomyocyte lineages throughout life and in response to injury in non-mammalian vertebrates 1 – 7 .…”

Hypoxia promotes a perinatal-like progenitor state in the adult murine epicardium

“…There is considerable research effort aimed at identifying factors that activate the adult epicardium in order to promote a beneficial recovery following cardiac injury 46,71,[78][79][80][81][82][83][84] . The embryonic and fetal hearts are physiologically hypoxic due to an underdeveloped cardiac vascular system and placenta restriction 12,[28][29][30][31]52,53,85,86 , whereas the hypoxic state is only maintained in the adult mammalian epicardium, as shown in this study and by others 34 . The epicardium has been shown to drive heart morphogenesis and serve as a reservoir of progenitors of non-cardiomyocyte lineages throughout life and in response to injury in non-mammalian vertebrates [1][2][3][4][5][6][7] .…”

SLC2A3 variants in familial and sporadic congenital heart diseases in a Chinese Yunnan population

“…Glucose, the primary nutrient of cells, is a critical regulator of growth in rapidly developing embryos 36 . As one of the highest energy consuming organs in mammals, the heart has to be provided with a high amount of energy as soon as it is functional in utero; during perinatal development, cellular energy metabolism of the cardiac tissue, including progenitors, switched from prenatal anaerobic glycolysis to postnatal fatty acid oxidation, which contributed to cardiac maturation 37 . SLC2A3 knockout mouse models were developed by several working groups 38,39 .…”

“…36 As one of the highest energy consuming organs in mammals, the heart has to be provided with a high amount of energy as soon as it is functional in utero; during perinatal development, cellular energy metabolism of the cardiac tissue, including progenitors, switched from prenatal anaerobic glycolysis to postnatal fatty acid oxidation, which contributed to cardiac maturation. 37 SLC2A3 knockout mouse models were developed by several working groups. 38,39 Heterozygosity resulted in early pregnancy loss in approximately 25% of affected mouse embryos, whereas a bi-allelic deletion of SLC2A3 was deleterious, leading to abortion on the twelfth day.…”