scholarly journals Transcriptional Regulation of Postnatal Cardiomyocyte Maturation and Regeneration

2021 ◽  
Vol 22 (6) ◽  
pp. 3288
Author(s):  
Stephanie L. Padula ◽  
Nivedhitha Velayutham ◽  
Katherine E. Yutzey
Keyword(s):  
Transcriptional Regulation ◽  
Cardiac Injury ◽  
Postnatal Period ◽  
Transitional Period ◽  
Therapeutic Implications ◽  
Hypertrophic Growth ◽  
Sarcomeric Protein ◽  
Transcriptional Changes ◽  
Protein Isoform ◽  
Isoform Switching

During the postnatal period, mammalian cardiomyocytes undergo numerous maturational changes associated with increased cardiac function and output, including hypertrophic growth, cell cycle exit, sarcomeric protein isoform switching, and mitochondrial maturation. These changes come at the expense of loss of regenerative capacity of the heart, contributing to heart failure after cardiac injury in adults. While most studies focus on the transcriptional regulation of embryonic or adult cardiomyocytes, the transcriptional changes that occur during the postnatal period are relatively unknown. In this review, we focus on the transcriptional regulators responsible for these aspects of cardiomyocyte maturation during the postnatal period in mammals. By specifically highlighting this transitional period, we draw attention to critical processes in cardiomyocyte maturation with potential therapeutic implications in cardiovascular disease.

scholarly journals Transcriptional regulation of structural and functional adaptations in a developing adulthood myocardium

2020 ◽  
Author(s):  
Sini Sunny ◽  
Anil Kumar Challa ◽  
Joseph Barchue ◽  
Muralidharan T. Ramamurthy ◽  
David K Crossman ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Signaling Pathways ◽  
Redox Homeostasis ◽  
Progressive Decline ◽  
Functional Changes ◽  
Adult Mice ◽  
Cycle Growth ◽  
Myocardial Development ◽  
Transcriptional Changes ◽  
Structural Adaptations

AbstractThe development of the heart follows a synergic action of several signaling pathways during gestational, pre- & postnatal stages. The current study aimed to investigate whether the myocardium experiences transcriptional changes during the transition from post-natal to adult hood stages. Herein, we used C57/Bl6/J mice at 4 (28-days; post-natal/PN) and 20 weeks (adulthood/AH) of ages and employed the next generation RNAseq (NGS) to profile the transcriptome and echocardiography analysis to monitor the structural/functional changes in the heart. NGS-based RNA-seq revealed that 1215 genes were significantly upregulated and 2549 were down regulated in the AH versus PN hearts, indicating a significant transcriptional change during this transition. A synchronized cardiac transcriptional regulation through cell cycle, growth hormones, redox homeostasis and metabolic pathways was noticed in both PN and AH hearts. Echocardiography reveals significant structural and functional (i.e. systolic/diastolic) changes during the transition of PN to adult stage. Particularly, a progressive decline in ejection fraction (EF) and cardiac output was observed in AH hearts. These structural adaptations are in line with critical signaling pathways that drive the maturation of heart during AH. Overall, we have presented a comprehensive transcriptomic analysis along with structural-functional relationship during the myocardial development in adult mice.

scholarly journals Neutrophil-Initiated Myocardial Inflammation and Its Modulation by B-Type Natriuretic Peptide: A Potential Therapeutic Target

2018 ◽  
Vol 20 (1) ◽  
pp. 129 ◽  
Author(s):  
Saifei Liu ◽  
Yuliy Chirkov ◽  
John Horowitz
Keyword(s):  
Heart Failure ◽  
Nadph Oxidase ◽  
Natriuretic Peptide ◽  
Tissue Injury ◽  
Diastolic Heart Failure ◽  
Cardiac Injury ◽  
Myocardial Inflammation ◽  
Inflammatory Disorder ◽  
Therapeutic Implications ◽  
Vasomotor Dysfunction

Activation of neutrophils is a critically important component of the innate immune response to bacterial and chemical stimuli, and culminates in the “neutrophil burst”, which facilitates neutrophil phagocytosis via the release of superoxide anion radical (O2−) from NADPH oxidase. Excessive and/or prolonged neutrophil activation results in substantial tissue injury and increases in vascular permeability—resulting in sustained tissue infiltration with neutrophils and monocytes, and persistent vasomotor dysfunction. Cardiovascular examples of such changes include acute and chronic systolic and diastolic heart failure (“heart failure with preserved ejection fraction”), and the catecholamine-induced inflammatory disorder takotsubo syndrome. We have recently demonstrated that B-type natriuretic peptide (BNP), acting via inhibition of activation of neutrophil NADPH oxidase, is an important negative modulator of the “neutrophil burst”, though its effectiveness in limiting tissue injury is partially lost in acute heart failure. The potential therapeutic implications of these findings, regarding the development of new means of treating both acute and chronic cardiac injury states, are discussed.

scholarly journals Troponin I Changes in Patients with Subarachnoid Hemorrhage

2018 ◽  
Vol 27 (2) ◽  
pp. 39-43
Author(s):  
A Sarker ◽  
MA Hoque ◽  
MMR Khan ◽  
MK Rahman ◽  
SM Alam ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Troponin I ◽  
Cardiac Injury ◽  
Neurological Injury ◽  
Enzyme Release ◽  
College Hospital ◽  
Cross Sectional ◽  
Therapeutic Implications ◽  
Patients At Risk ◽  
Ctni Level

Background : Subarachnoid hemorrhage (SAH) is a catastrophic neurological event. Aside from its neurological morbidities, SAH is associated with significant medical complications. Cardiac manifestations are common and can impact morbidity and mortality in SAH patients. Myocardial enzyme release occur frequently after Subarachnoid hemorrhage that reflect adverse intracranial events .These changes often are unrecognized or misinterpreted, potentially placing patients at risk for inappropriate management.Objective : The aim of this study was to assess Troponin I changes after acute SAH and these changes were compared with neurological severity. The result of the study might be helpful for better understanding diagnostic and therapeutic implications of acute neurocardiogenic injury after SAH.Patients and methods : This cross sectional descriptive study was conducted over 30 patients with SAH in medicine, neuromedicine and intensive care unit of Rajshahi Medical College Hospital during the period of January 2015 to December 2016. Predictor variables reflecting demographic (age, sex, occupation), hemodynamic (pulse, systolic and diastolic blood pressure) and neurological (WFNS score) informations were recorded. We evaluated their cTnI level, which had been measured at admission. A cTnI level above 0.12 ng/ml was defined as an indicator of cardiac injury following SAH.Results : Out of 30 patients 26.7% were both in between 40-49 years and 60-69 years age group & 50% were male and 50% were female. Among the risk factors 60% of patient had history of hypertension, 40% smoking, 10% Diabetes mellitus and 3.3% alcohol abuse. On admission the mean GCS was 12.53±2.69,. The most frequently occurring WFNS grading were grade 1 and grade 4 (both were 43.3% of patients). Out of Thirty, 43.3% of patients demonstrated elevations of Troponin I. WFNS score ≥ 3 (92.3%, p = <0.001) significantly correlated with elevated Troponin I concentration.Conclusion : serum troponin I reveal a higher incidence of myocardial injury in patients with SAH. The present study also demonstrates that raised serum cTnI is associated with more severe neurological injury. These findings support a neurocardiogenic cause of cardiac injury after SAH.TAJ 2014; 27(2): 39-43

scholarly journals Role of PTEN-less in cardiac injury, hypertrophy and regeneration

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Tian Liang ◽  
Feng Gao ◽  
Jinghai Chen
Keyword(s):  
Stress Responses ◽  
Cardiac Fibrosis ◽  
Cardiac Development ◽  
Heart Function ◽  
Cardiac Injury ◽  
Therapeutic Effects ◽  
Hypertrophic Growth ◽  
Dual Specificity ◽  
Cellular Factors ◽  
Physiological Homeostasis

AbstractCardiovascular diseases are the leading cause of death worldwide. Cardiomyocytes are capable of coordinated contractions, which are mainly responsible for pumping blood. When cardiac stress occurs, cardiomyocytes undergo transition from physiological homeostasis to hypertrophic growth, proliferation, or apoptosis. During these processes, many cellular factors and signaling pathways participate. PTEN is a ubiquitous dual-specificity phosphatase and functions by dephosphorylating target proteins or lipids, such as PIP3, a second messenger in the PI3K/AKT signaling pathway. Downregulation of PTEN expression or inhibiting its biologic activity improves heart function, promotes cardiomyocytes proliferation, reduces cardiac fibrosis as well as dilation, and inhibits apoptosis following ischemic stress such as myocardial infarction. Inactivation of PTEN exhibits a potentially beneficial therapeutic effects against cardiac diseases. In this review, we summarize various strategies for PTEN inactivation and highlight the roles of PTEN-less in regulating cardiomyocytes during cardiac development and stress responses.

Abstract 13391: Cardiomyocyte Cell Cycling, Maturation, and Growth by Multinucleation in Postnatal Swine

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Nivedhitha Velayutham ◽  
Christina M Alfieri ◽  
Emma J Agnew ◽  
Kyle W Riggs ◽  
Richard S Baker ◽  
...  
Keyword(s):  
Ventricular Myocardium ◽  
Postnatal Period ◽  
Left Ventricular ◽  
Cell Junctions ◽  
Left Ventricular Myocardium ◽  
Cross Sectional ◽  
Hypertrophic Growth ◽  
Species Response ◽  
Neuronal Remodeling ◽  
Cell Cycling

Background: Rodent cardiomyocytes (CM) undergo mitotic arrest and decline of mononucleated-diploid population post-birth, which are implicated in neonatal loss of heart regenerative potential. However, the dynamics of postnatal CM maturation are largely unknown in swine, despite a similar neonatal cardiac regenerative capacity as rodents. Here, we provide a comprehensive analysis of postnatal cardiac maturation in swine, including CM cell cycling, multinucleation and hypertrophic growth, as well as non-CM cardiac factors such as extracellular matrix (ECM), immune cells, capillaries, and neurons. Our study reveals discordance in postnatal pig heart maturational events compared to rodents. Methods and Results: Left-ventricular myocardium from White Yorkshire-Landrace pigs at postnatal day (P)0 to 6 months (6mo) was analyzed. Mature cardiac sarcomeric characteristics, such as fetal TNNI1 repression and CX43 co-localization to cell junctions, were not evident until P30 in pigs. In CMs, appreciable binucleation is observed by P7, with extensive multinucleation (4-16 nuclei per CM) beyond P15. Individual CM nuclei remain predominantly diploid at all ages. CM mononucleation at ~50% incidence is observed at P7-P15, and CM mitotic activity is measurable up to 2mo. CM cross-sectional area does not increase until 2mo-6mo in pigs, though longitudinal CM growth proportional to multinucleation occurs after P15. RNAseq analysis of neonatal pig left ventricles showed increased expression of ECM maturation, immune signaling, neuronal remodeling, and reactive oxygen species response genes, highlighting significance of the non-CM milieu in postnatal mammalian heart maturation. Conclusions: CM maturational events such as decline of mononucleation and cell cycle arrest occur over a 2-month postnatal period in pigs, despite reported loss of heart regenerative potential by P3. Moreover, CMs grow primarily by multinucleation and longitudinal hypertrophy in older pigs, distinct from mice and humans. These differences are important to consider for preclinical testing of cardiovascular therapies using swine, and may offer opportunities to study aspects of heart regeneration unavailable in other models.

scholarly journals Polyploidy in Cardiomyocytes

2020 ◽  
Vol 126 (4) ◽  
pp. 552-565 ◽  
Author(s):  
Wouter Derks ◽  
Olaf Bergmann
Keyword(s):  
Cardiac Injury ◽  
Physiological Role ◽  
Cell Types ◽  
Cell Number ◽  
The Body ◽  
Cardiomyocyte Hypertrophy ◽  
Heart Regeneration ◽  
Cardiomyocyte Proliferation ◽  
Hypertrophic Growth

The hallmark of most cardiac diseases is the progressive loss of cardiomyocytes. In the perinatal period, cardiomyocytes still proliferate, and the heart shows the capacity to regenerate upon injury. In the adult heart, however, the actual rate of cardiomyocyte renewal is too low to efficiently counteract substantial cell loss caused by cardiac injury. In mammals, cardiac growth by cell number expansion changes to growth by cardiomyocyte enlargement soon after birth, coinciding with a period in which most cardiomyocytes increase their DNA content by multinucleation and nuclear polyploidization. Although cardiomyocyte hypertrophy is often associated with these processes, whether polyploidy is a prerequisite or a consequence of hypertrophic growth is unclear. Both the benefits of cardiomyocyte enlargement over proliferative growth of the heart and the physiological role of polyploidy in cardiomyocytes are enigmatic. Interestingly, hearts in animal species with substantial cardiac regenerative capacity dominantly comprise diploid cardiomyocytes, raising the hypothesis that cardiomyocyte polyploidy poses a barrier for cardiomyocyte proliferation and subsequent heart regeneration. On the contrary, there is also evidence for self-duplication of multinucleated myocytes, suggesting a more complex picture of polyploidy in heart regeneration. Polyploidy is not restricted to the heart but also occurs in other cell types in the body. In this review, we explore the biological relevance of polyploidy in different species and tissues to acquire insight into its specific role in cardiomyocytes. Furthermore, we speculate about the physiological role of polyploidy in cardiomyocytes and how this might relate to renewal and regeneration.

c-Fos-activated synthesis of nuclear phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] promotes global transcriptional changes

2014 ◽  
Vol 461 (3) ◽  
pp. 521-530 ◽  
Author(s):  
Gabriel O. Ferrero ◽  
Marianne L. Renner ◽  
Germán A. Gil ◽  
Lucia Rodríguez-Berdini ◽  
Beatriz L. Caputto
Keyword(s):  
Transcriptional Regulation ◽  
Phospholipid Synthesis ◽  
Transcriptional Changes

c-Fos promotes transcriptional changes by activating phosphatidylinositol-4,5-bisphosphate synthesis in the nucleus. Regulatory transcriptional functions of c-Fos can now be extended to its phospholipid synthesis activator capacity, which means that new mechanisms of transcriptional regulation can be envisaged.

scholarly journals The role of microRNAs in cardiac development and regenerative capacity

2016 ◽  
Vol 310 (5) ◽  
pp. H528-H541 ◽  
Author(s):  
Michael G. Katz ◽  
Anthony S. Fargnoli ◽  
Andrew P. Kendle ◽  
Roger J. Hajjar ◽  
Charles R. Bridges
Keyword(s):  
Recent Progress ◽  
Cardiac Development ◽  
Terminal Differentiation ◽  
Postnatal Period ◽  
The Novel ◽  
Cardiomyocyte Differentiation ◽  
Regenerative Capacity ◽  
Hypertrophic Growth ◽  
Differentiation And Proliferation

The mammalian heart has long been considered to be a postmitotic organ. It was thought that, in the postnatal period, the heart underwent a transition from hyperplasic growth (more cells) to hypertrophic growth (larger cells) due to the conversion of cardiomyocytes from a proliferative state to one of terminal differentiation. This hypothesis was gradually disproven, as data were published showing that the myocardium is a more dynamic tissue in which cardiomyocyte karyokinesis and cytokinesis produce new cells, leading to the hyperplasic regeneration of some of the muscle mass lost in various pathological processes. microRNAs have been shown to be critical regulators of cardiomyocyte differentiation and proliferation and may offer the novel opportunity of regenerative hyperplasic therapy. Here we summarize the relevant processes and recent progress regarding the functions of specific microRNAs in cardiac development and regeneration.

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