Glucocorticoids, antenatal corticosteroid therapy and fetal heart maturation

Agnew, Emma J; Ivy,; Stock, Sarah; Chapman, Karen

doi:10.1530/jme-18-0077

Cited by 53 publications

(45 citation statements)

References 129 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In several studies conducted in both humans and other animals, premature birth was found to be associated with abnormal CM hypertrophy and nucleation and premature cell cycle cessation (Bensley et al 2010(Bensley et al , 2018Aye et al 2017). As a caveat, however, patients in these studies were often treated antenatally and/or postnatally with corticosteroids, which may in turn affect CM maturation (Agnew et al 2017).…”

Section: Initiation Of CM Maturationmentioning

confidence: 99%

Regulation of cardiomyocyte maturation during critical perinatal window

Kannan

Kwon

2019

The Journal of Physiology

View full text Add to dashboard Cite

A primary limitation in the use of pluripotent stem cell-derived cardiomyocytes (PSC-CMs) for both patient health and scientific investigation is the failure of these cells to achieve full functional maturity. In vivo, cardiomyocytes undergo numerous adaptive structural, functional and metabolic changes during maturation. By contrast, PSC-CMs fail to fully undergo these developmental processes, instead remaining arrested at an embryonic stage of maturation. There is thus a significant need to understand the biological processes underlying proper CM maturation in vivo. Here, we discuss what is known regarding the initiation and coordination of CM maturation. We postulate that there is a critical perinatal window, ranging from embryonic day 18.5 to postnatal day 14 in mice, in which the maturation process is exquisitely sensitive to perturbation. While the initiation mechanisms of this process are unknown, it is increasingly clear that maturation proceeds through interconnected regulatory circuits that feed into one another to coordinate concomitant structural, functional and metabolic CM maturation. We highlight PGC1α, SRF and the MEF2 family as transcription factors that may potentially mediate this cross-talk. We lastly discuss several emerging technologies that will facilitate future studies into the mechanisms of CM maturation. Further study will not only produce a better understanding of its key processes, but provide practical insights into developing a robust strategy to produce mature PSC-CMs. Abstract figure legendHere, we postulate that there is a critical window, ranging from embryonic day 18.5 to postnatal day 14 in mice, in which interconnected regulatory circuits enable coordinated, concomitant structural, functional and metabolic cardiomyocyte maturation.

show abstract

Section: Initiation Of CM Maturationmentioning

confidence: 99%

Regulation of cardiomyocyte maturation during critical perinatal window

Kannan

Kwon

2019

The Journal of Physiology

View full text Add to dashboard Cite

show abstract

“…Several studies found that P*M CMs possess enhanced protein synthesis to match the high demand for muscle fibers and adenosine triphosphate (ATP) metabolism at high speed [41,42]. AMPK are the major regulator of protein synthesis through mTOR-dependent or -independent mechanism.…”

Section: Discussionmentioning

confidence: 99%

Multinucleated polyploid cardiomyocytes undergo an enhanced adaptability to hypoxia via mitophagy

Jiang

Wang

Peng

et al. 2020

Journal of Molecular and Cellular Cardiology

View full text Add to dashboard Cite

There is a large subpopulation of multinucleated polyploid cardiomyocytes (M*Pc CMs) in the adult mammalian heart. However, the pathophysiological significance of increased M*Pc CMs in heart disease is poorly understood. We sought to determine the pathophysiological significance of increased M*Pc CMs during hypoxia adaptation. Methods and results: A model of hypoxia-induced cardiomyocyte (CM) multinucleation and polyploidization was established and found to be associated with less apoptosis and less reactive oxygen species (ROS) production. Compared to mononucleated diploid CMs (1*2c CMs), tetraploid CMs (4c CMs) exhibited better mitochondria quality control via increased mitochondrial autophagy (mitophagy). RNA-seq revealed Prkaa2, the gene for AMPKα2, was the most obviously up-regulated autophagy-related gene. Knockdown of AMPKα2 increased apoptosis and ROS production and suppressed mitophagy in 4c CMs compared to 1*2c CMs. Rapamycin, an autophagy activator, alleviated the adverse effect of AMPKα2 knockdown. Furthermore, silencing PINK1 also increased apoptosis and ROS in 4c CMs and weakened the adaptive superiority of 4c CMs. Finally, AMPKα2 −/− mutant mice exhibited exacerbation of apoptosis and ROS production via decreases in AMPKα2-mediated mitophagy in 4c CMs compared to 1*2c CMs during hypoxia. Conclusions: Compared to 1*2c CMs, hypoxia-induced 4c CMs exhibited enhanced mitochondria quality control and less apoptosis via AMPKα2-mediated mitophagy. These results suggest that multinucleation and polyploidization allow CM to better adapt to stress via enhanced mitophagy. In addition, activation of AMPKα2 may be a promising target for myocardial hypoxia-related diseases.

show abstract

“…In humans, prenatal exposure to glucocorticoids improves cardiovascular function in the newborn immediately after birth [ 163 , 229 , 230 , 231 , 232 ]. Antenatal corticosteroid therapy (ACT) of a potent synthetic glucocorticoid mimics the activity of endogenous glucocorticoids and is prescribed to women to decrease the risk of preterm delivery and to mature fetal organs, including the heart [ 233 ]. The goal of ACT is to improve the survival of preterm infants and decrease neonatal morbidity.…”

Section: Recent Advances In Bioactive Lipids In Cardiac Diseasementioning

confidence: 99%

Bioactive Lipid Signaling in Cardiovascular Disease, Development, and Regeneration

Wasserman

Venkatesan

Aguirre

2020

Cells

View full text Add to dashboard Cite

Cardiovascular disease (CVD) remains a leading cause of death globally. Understanding and characterizing the biochemical context of the cardiovascular system in health and disease is a necessary preliminary step for developing novel therapeutic strategies aimed at restoring cardiovascular function. Bioactive lipids are a class of dietary-dependent, chemically heterogeneous lipids with potent biological signaling functions. They have been intensively studied for their roles in immunity, inflammation, and reproduction, among others. Recent advances in liquid chromatography-mass spectrometry techniques have revealed a staggering number of novel bioactive lipids, most of them unknown or very poorly characterized in a biological context. Some of these new bioactive lipids play important roles in cardiovascular biology, including development, inflammation, regeneration, stem cell differentiation, and regulation of cell proliferation. Identifying the lipid signaling pathways underlying these effects and uncovering their novel biological functions could pave the way for new therapeutic strategies aimed at CVD and cardiovascular regeneration.

show abstract

Glucocorticoids, antenatal corticosteroid therapy and fetal heart maturation

Cited by 53 publications

References 129 publications

Regulation of cardiomyocyte maturation during critical perinatal window

Regulation of cardiomyocyte maturation during critical perinatal window

Multinucleated polyploid cardiomyocytes undergo an enhanced adaptability to hypoxia via mitophagy

Bioactive Lipid Signaling in Cardiovascular Disease, Development, and Regeneration

Contact Info

Product

Resources

About