Regulatory Mechanisms That Guide the Fetal to Postnatal Transition of Cardiomyocytes

Abstract

Heart disease remains a global leading cause of death and disability, necessitating a comprehensive understanding of the heart's development, repair, and dysfunction. This review surveys recent discoveries that explore the developmental transition of proliferative fetal cardiomyocytes into hypertrophic postnatal cardiomyocytes, a process yet to be well-defined. This transition is key to the heart's growth and has promising therapeutic potential, particularly for congenital or acquired heart damage, such as myocardial infarctions. Although significant progress has been made, much work is needed to unravel the complex interplay of signaling pathways that regulate cardiomyocyte proliferation and hypertrophy. This review provides a detailed perspective for future research directions aimed at the potential therapeutic harnessing of the perinatal heart transitions.

Keywords: fetal to postnatal development; hypertrophy and proliferation; micro-RNA; signaling pathways (mTOR, Hippo, YAP/TAZ); therapeutic potential.

Figure 1

The transitional program: Reprogramming embryonic cardiomyocytes into postnatal cardiomyocytes. (A) Embryonic heart growth is primarily due to the high proliferative capacity of fetal cardiomyocytes, whereas postnatal heart growth is associated with binucleated cardiomyocyte hypertrophy. (B) Linking the fetal cardiogenomic program (green) to the postnatal cardiogenomic program (red). The transitional program (yellow) mediates the passage of proliferative fetal cardiomyocytes to exit the cell cycle prematurely to form binucleated hypertrophic cardiomyocytes.

Figure 2

The transition of mammalian cardiomyocyte (CM) growth signaling pathways that convert proliferative fetal cardiomyocytes into hypertrophic adult cardiomyocytes. Top panel. The Hippo pathway is the primary fetal cardiomyogenic hyperplasia program (green) that regulates fetal CM number prior to birth (0 d). Birth triggers the perinatal transition program (yellow) that facilitates the conversion of fetal CM into adult hypertrophic CMs (red). MicroRNAs are excellent candidate molecules that propagate the CM perinatal transition. The mTOR pathway is the principal pathway that controls CM physiological hypertrophy. 0 d = time of birth and 14 d = 14 days post-birth. Bottom Panel: Highlights the differences between fetal (green) and adult (red) cardiomyocytes.