scholarly journals Neuregulin-1, in a Conducive Milieu with Wnt/BMP/Retinoic Acid, Prolongs the Epicardial-Mediated Cardiac Regeneration Capacity of Neonatal Heart Explants

2021 ◽  
Vol 17 (1) ◽  
Keyword(s):  
Retinoic Acid ◽  
Cardiac Regeneration ◽  
Regeneration Capacity ◽  
Neuregulin 1 ◽  
Neonatal Heart

Abstract 20134: Transcriptional Profiling Identifies Candidate Regulators of Neonatal Heart Regeneration

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Caitlin O’Meara ◽  
Joseph Wamstad ◽  
Laurie Boyer ◽  
Richard T Lee
Keyword(s):  
Cell Cycle ◽  
Transcriptional Profiling ◽  
Cardiac Regeneration ◽  
Heart Regeneration ◽  
Transcriptional Signature ◽  
Adult Mice ◽  
Neonatal Heart ◽  
Sirna Knockdown

Some higher organisms, such as zebrafish and neonatal mice, are capable of complete and sufficient regeneration of the myocardium following injury, which is thought to occur primarily by proliferation of pre-existing cardiomyocytes. Although adult humans and adult mice lack this cardiac regeneration potential, there is great interest in understanding how regeneration can occur in the heart so that we can activate this process in humans suffering from heart failure. The aim of our study was to identify mechanisms by which mature, post-mitotic adult cardiomyocytes can re-enter the cell cycle to ultimately facilitate heart regeneration following injury. We derived a core transcriptional signature of injury-induced cardiomyocyte regeneration in mouse by comparing global transcriptional programs in a dynamic model of in vitro and in vivo cardiomyocyte differentiation and in an in vitro cardiomyocyte explant model, as well as a neonatal heart resection model. We identified a panel of transcription factors, growth factors, and cytokines, whose expression significantly correlated with the differentiated state of the cell in all datasets examined, suggesting that these factors play a role in regulating cardiomyocyte cell state. Furthermore, potential upstream regulators of core differentially expressed networks were identified using Ingenuity Pathway Analysis and we found that one predicted regulator, interleukin-13 (IL13), significantly induced cardiomyocyte cell cycle activity and STAT6/STAT3 signaling in vitro. siRNA knockdown experiments demonstrated that STAT3/periostin and STAT6 signaling are critical for cardiomyocyte cell cycle activity in response to IL13. These data reveal novel insights into the transcriptional regulation of mammalian heart regeneration and provide the founding circuitry for identifying potential regulators for stimulating cardiomyocyte cell cycle activity.

scholarly journals Mechanistic basis of neonatal heart regeneration revealed by transcriptome and histone modification profiling

2019 ◽  
Vol 116 (37) ◽  
pp. 18455-18465 ◽  
Author(s):  
Zhaoning Wang ◽  
Miao Cui ◽  
Akansha M. Shah ◽  
Wenduo Ye ◽  
Wei Tan ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Rna Binding ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cardiac Regeneration ◽  
Later Life ◽  
Heart Regeneration ◽  
Cardiomyocyte Proliferation ◽  
Neonatal Heart ◽  
Short Period

The adult mammalian heart has limited capacity for regeneration following injury, whereas the neonatal heart can readily regenerate within a short period after birth. To uncover the molecular mechanisms underlying neonatal heart regeneration, we compared the transcriptomes and epigenomes of regenerative and nonregenerative mouse hearts over a 7-d time period following myocardial infarction injury. By integrating gene expression profiles with histone marks associated with active or repressed chromatin, we identified transcriptional programs underlying neonatal heart regeneration, and the blockade to regeneration in later life. Our results reveal a unique immune response in regenerative hearts and a retained embryonic cardiogenic gene program that is active during neonatal heart regeneration. Among the unique immune factors and embryonic genes associated with cardiac regeneration, we identified Ccl24, which encodes a cytokine, and Igf2bp3, which encodes an RNA-binding protein, as previously unrecognized regulators of cardiomyocyte proliferation. Our data provide insights into the molecular basis of neonatal heart regeneration and identify genes that can be modulated to promote heart regeneration.

The roles of signaling pathways in cardiac regeneration

2021 ◽  
Vol 28 ◽  
Author(s):  
Amir Valizadeh ◽  
Samira Asghari ◽  
Parinaz Mansouri ◽  
Forough Alemi ◽  
Maryam Majidinia ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Animal Species ◽  
Cell Communication ◽  
Cardiac Regeneration ◽  
Cardiac Repair ◽  
Regeneration Capacity ◽  
Disease Treatment ◽  
Model Studies ◽  
Vegf Signaling

: In recent years, knowledge of cardiac regeneration mechanisms has dramatically expanded. Regeneration can replace lost parts of organs, common among animal species. The heart is commonly considered an organ with terminal development, which has no reparability potential during post-natal life; however, some intrinsic regeneration capacity has been reported for cardiac muscle, which opens novel avenues in cardiovascular disease treatment. Different endogenous mechanisms were studied for cardiac repairing and regeneration in recent decades. Survival, proliferation, inflammation, angiogenesis, cell-cell communication, cardiomyogenesis, and anti-aging pathways are the most important mechanisms that have been studied in this regard. Several in vitro and animal model studies focused on proliferation induction for cardiac regeneration reported promising results. These studies have mainly focused on promoting proliferation signaling pathways and demonstrated various signaling pathways such as Wnt, PI3K/Akt, IGF-1, TGF-β, Hippo, and VEGF signaling cardiac regeneration. Therefore, in this review, we intended to discuss the connection between different critical signaling pathways in cardiac repair and regeneration.

scholarly journals Neuregulin-1 Administration Protocols Sufficient for Stimulating Cardiac Regeneration in Young Mice Do Not Induce Somatic, Organ, or Neoplastic Growth

PLoS ONE ◽  
2016 ◽  
Vol 11 (5) ◽  
pp. e0155456 ◽  
Author(s):  
Balakrishnan Ganapathy ◽  
Nikitha Nandhagopal ◽  
Brian D. Polizzotti ◽  
David Bennett ◽  
Alparslan Asan ◽  
...  
Keyword(s):  
Cardiac Regeneration ◽  
Neuregulin 1 ◽  
Neoplastic Growth ◽  
Young Mice

scholarly journals Reiterative Mechanisms of Retinoic Acid Signaling during Vertebrate Heart Development

2019 ◽  
Vol 7 (2) ◽  
pp. 11 ◽  
Author(s):  
Eliyahu Perl ◽  
Joshua S. Waxman
Keyword(s):  
Retinoic Acid ◽  
Heart Development ◽  
Congenital Heart ◽  
Heart Defects ◽  
Cardiac Regeneration ◽  
Retinoic Acid Signaling ◽  
Vertebrate Development ◽  
History Of Research ◽  
History Of ◽  
Synthesis And Degradation

Tightly-regulated levels of retinoic acid (RA) are critical for promoting normal vertebrate development. The extensive history of research on RA has shown that its proper regulation is essential for cardiac progenitor specification and organogenesis. Here, we discuss the roles of RA signaling and its establishment of networks that drive both early and later steps of normal vertebrate heart development. We focus on studies that highlight the drastic effects alternative levels of RA have on early cardiomyocyte (CM) specification and cardiac chamber morphogenesis, consequences of improper RA synthesis and degradation, and known effectors downstream of RA. We conclude with the implications of these findings to our understanding of cardiac regeneration and the etiologies of congenital heart defects.

Abstract 13368: Acetylation of VGLL4 Tdu Domain Modulates Its Activity to Regulate Postnatal Cardiac Growth (Best of Basic Science Abstract)

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Zhiqiang Lin ◽  
Haidong Guo ◽  
Pingzhu Zhou ◽  
Qing Ma ◽  
Jin Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Point Mutation ◽  
Basic Science ◽  
Binding Protein ◽  
Cardiac Regeneration ◽  
Hippo Signaling ◽  
Cardiac Growth ◽  
Neonatal Heart ◽  
Terminal Effector

Mammalian cardiomyocytes (CM) largely exit the cell cycle shortly after birth, limiting the heart’s capacity to recover from injury. The mechanisms that enforce neonatal CM cell cycle withdrawal are largely unknown. CM proliferation is stimulated by interaction of the co-activator YAP, the terminal effector of Hippo signaling, with the transcription factor TEAD1, but YAP’s mitogenic potency declines in the adult compared to fetal or newborn heart. Here we show that VGLL4, a CM-enriched TEAD1 binding protein, inhibits CM proliferation by competing with YAP for TEAD1 binding. Moreover, VGLL4 activity is regulated by acetylation of the lysine 225 (K225) residing in its first Tondu (Tdu) domain. Acetylation at K225 antagonized its interaction with TEAD1 in the neonatal heart. Overexpression of VGLL4 with a point mutation that blocks its acetylation enhanced VGLL4-TEAD1 interaction and limited CM proliferation, resulting in lethal cardiac hypoplasia. Our study defines a novel acetylation-mediated, VGLL4-dependent switch that regulates Hippo-YAP signaling and that restrains CM proliferation. These insights may enable more effective approaches to cardiac regeneration.

scholarly journals Cardiac Regeneration Therapies – Targeting Neuregulin 1 Signalling

2016 ◽  
Vol 25 (1) ◽  
pp. 4-7 ◽  
Author(s):  
Richard P. Harvey ◽  
Katharina Wystub-Lis ◽  
Gonzalo del Monte-Nieto ◽  
Robert M. Graham ◽  
Eldad Tzahor
Keyword(s):  
Cardiac Regeneration ◽  
Neuregulin 1

scholarly journals Cell-Free Approaches and Therapeutic Biomolecules for Cardiac Regeneration

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 161
Author(s):  
Mariann Gyöngyösi
Keyword(s):  
Stem Cells ◽  
Human Heart ◽  
Cardiac Regeneration ◽  
Cardiac Stem Cells ◽  
Regeneration Capacity ◽  
Cardiac Progenitors ◽  
Human Organs ◽  
Adult Human

In contrast with some adult human organs, such as liver or skin, the adult human heart shows very limited self-regeneration capacity, attributed to the negligible presence of resident cardiac stem cells or cardiac progenitors [...]

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