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adult cardiomyocyte proliferation

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https://www.readbyqxmd.com/read/28916735/functional-screening-in-human-cardiac-organoids-reveals-a-metabolic-mechanism-for-cardiomyocyte-cell-cycle-arrest
#1
Richard J Mills, Drew M Titmarsh, Xaver Koenig, Benjamin L Parker, James G Ryall, Gregory A Quaife-Ryan, Holly K Voges, Mark P Hodson, Charles Ferguson, Lauren Drowley, Alleyn T Plowright, Elise J Needham, Qing-Dong Wang, Paul Gregorevic, Mei Xin, Walter G Thomas, Robert G Parton, Lars K Nielsen, Bradley S Launikonis, David E James, David A Elliott, Enzo R Porrello, James E Hudson
The mammalian heart undergoes maturation during postnatal life to meet the increased functional requirements of an adult. However, the key drivers of this process remain poorly defined. We are currently unable to recapitulate postnatal maturation in human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs), limiting their potential as a model system to discover regenerative therapeutics. Here, we provide a summary of our studies, where we developed a 96-well device for functional screening in human pluripotent stem cell-derived cardiac organoids (hCOs)...
September 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28895403/injectable-carbon-nanotube-functionalized-reverse-thermal-gel-promotes-cardiomyocytes-survival-and-maturation
#2
Brisa Peña, Susanna Bosi, Brian A Aguado, Daniele Borin, Nikki L Farnsworth, Evgenia Dobrinskikh, Teisha J Rowland, Valentina Martinelli, Mark Jeong, Matthew R G Taylor, Carlin S Long, Robin Shandas, Orfeo Sbaizero, Maurizio Prato, Kristi S Anseth, Daewon Park, Luisa Mestroni
The ability of the adult heart to regenerate cardiomyocytes (CMs) lost after injury is limited, generating interest in developing efficient cell-based transplantation therapies. Rigid carbon nanotubes (CNTs) scaffolds have been used to improve CMs viability, proliferation, and maturation, but they require undesirable invasive surgeries for implantation. To overcome this limitation, we developed an injectable reverse thermal gel (RTG) functionalized with CNTs (RTG-CNT) that transitions from a solution at room temperature to a three-dimensional (3D) gel-based matrix shortly after reaching body temperature...
September 12, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28895052/the-effects-of-periostin-in-a-rat-model-of-isoproterenol-mediated-cardiotoxicity
#3
Mahmut Sözmen, Alparslan K Devrim, Yonca B Kabak, Tuba Devrim, Mert Sudagidan
Periostin is an extracellular matrix protein from fasciclin family, and it plays an important role in the cell adhesion, migration, and growth of the organism. Periostin prevents apoptosis while stimulating cardiomyocytes. The present study was designed to investigate cardioprotective effects of the recombinant murine periostin peptide administration in a rat model of isoproterenol (ISO)-induced myocardial injury. The experiment was performed on 84 adult male Sprague Dawley rats in 4 groups (n = 21): control group (1), periostin-treated group (2), ISO-treated group (3), and ISO + periostin-treated group (4)...
September 11, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28878117/tead1-is-required-for-maintaining-adult-cardiomyocyte-function-and-its-loss-results-in-lethal-dilated-cardiomyopathy
#4
Ruya Liu, Jeongkyung Lee, Byung S Kim, Qiongling Wang, Samuel K Buxton, Nikhil Balasubramanyam, Jean J Kim, Jianrong Dong, Aijun Zhang, Shumin Li, Anisha A Gupte, Dale J Hamilton, James F Martin, George G Rodney, Cristian Coarfa, Xander Ht Wehrens, Vijay K Yechoor, Mousumi Moulik
Heart disease remains the leading cause of death worldwide, highlighting a pressing need to identify novel regulators of cardiomyocyte (CM) function that could be therapeutically targeted. The mammalian Hippo/Tead pathway is critical in embryonic cardiac development and perinatal CM proliferation. However, the requirement of Tead1, the transcriptional effector of this pathway, in the adult heart is unknown. Here, we show that tamoxifen-inducible adult CM-specific Tead1 ablation led to lethal acute-onset dilated cardiomyopathy, associated with impairment in excitation-contraction coupling...
September 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/28873339/non-invasive-strategies-for-stimulating-endogenous-repair-and-regenerative-mechanisms-in-the-damaged-heart
#5
REVIEW
Fiona C Lewis, Siri Deva Kumar, Georgina M Ellison-Hughes
The adult myocardium, including human, harbours a population of resident multi-potent cardiac stem cells (CSCs), which when stimulated under the right conditions can give rise to new cardiomyocytes and vasculature. Elucidation of the cellular and molecular mechanisms that govern CSC biology and their role in myocardial regeneration will allow the design and development of optimal therapeutic interventions. It is now evident that different growth factors and cytokines govern CSC survival, proliferation, migration and differentiation, as well as playing a role in activating cardiac repair mechanisms such as improving angiogenesis, cardiomyocyte survival and limiting fibrosis...
September 2, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28819000/hypoxia-induced-myocardial-regeneration
#6
Wataru Kimura, Yuji Nakada, Hesham A Sadek
The underlying cause of systolic heart failure is the inability of the adult mammalian heart to regenerate damaged myocardium. In contrast, some vertebrate species and immature mammals are capable of full cardiac regeneration following multiple types of injury through cardiomyocyte proliferation. Little is known about what distinguishes proliferative cardiomyocytes from terminally differentiated, non-proliferative cardiomyocytes. Recently, several reports have suggested that oxygen metabolism and oxidative stress play a pivotal role in regulating the proliferative capacity of mammalian cardiomyocytes...
August 17, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28817660/cited4-is-related-to-cardiogenic-induction-and-maintenance-of-proliferation-capacity-of-embryonic-stem-cell-derived-cardiomyocytes-during-in-vitro-cardiogenesis
#7
Junichiro Miake, Tomomi Notsu, Katsumi Higaki, Kyoko Hidaka, Takayuki Morisaki, Kazuhiro Yamamoto, Ichiro Hisatome
Cardiac progenitor cells have a limited proliferative capacity. The CREB-binding protein/p300-interacting transactivator, with the Glu/Asp-rich carboxy-terminal domain (Cited) gene family, regulates gene transcription. Increased expression of the Cited4 gene in an adult mouse is associated with exercise-induced cardiomyocyte hypertrophy and proliferation. However, the expression patterns and functional roles of the Cited4 gene during cardiogenesis are largely unknown. Therefore, in the present study, we investigated the expression patterns and functional roles of the Cited4 gene during in vitro cardiogenesis...
2017: PloS One
https://www.readbyqxmd.com/read/28783163/frequency-of-mononuclear-diploid-cardiomyocytes-underlies-natural-variation-in-heart-regeneration
#8
Michaela Patterson, Lindsey Barske, Ben Van Handel, Christoph D Rau, Peiheng Gan, Avneesh Sharma, Shan Parikh, Matt Denholtz, Ying Huang, Yukiko Yamaguchi, Hua Shen, Hooman Allayee, J Gage Crump, Thomas I Force, Ching-Ling Lien, Takako Makita, Aldons J Lusis, S Ram Kumar, Henry M Sucov
Adult mammalian cardiomyocyte regeneration after injury is thought to be minimal. Mononuclear diploid cardiomyocytes (MNDCMs), a relatively small subpopulation in the adult heart, may account for the observed degree of regeneration, but this has not been tested. We surveyed 120 inbred mouse strains and found that the frequency of adult mononuclear cardiomyocytes was surprisingly variable (>7-fold). Cardiomyocyte proliferation and heart functional recovery after coronary artery ligation both correlated with pre-injury MNDCM content...
September 2017: Nature Genetics
https://www.readbyqxmd.com/read/28745540/p53-and-mdm2-act-synergistically-to-maintain-cardiac-homeostasis-and-mediate-cardiomyocyte-cell-cycle-arrest-through-a-network-of-micrornas
#9
Shanna Stanley-Hasnain, Ludger Hauck, Daniela Grothe, Roozbeh Aschar-Sobbi, Sanja Beca, Jagdish Butany, Peter H Backx, Tak W Mak, Filio Billia
Defining the roadblocks responsible for cell cycle arrest in adult cardiomyocytes lies at the core of developing cardiac regenerative therapies. p53 and Mdm2 are crucial mediators of cell cycle arrest in proliferative cell types, however, little is known about their function in regulating homeostasis and proliferation in terminally differentiated cell types, like cardiomyocytes. To explore this, we generated a cardiac-specific conditional deletion of p53 and Mdm2 (DKO) in adult mice. Herein we describe the development of a dilated cardiomyopathy, in the absence of cardiac hypertrophy...
2017: Cell Cycle
https://www.readbyqxmd.com/read/28745213/emerging-roles-of-meis1-in-cardiac-regeneration-stem-cells-and-cancer
#10
Merve Aksoz, Raife Dilek Turan, Esra Albayrak, Fatih Kocabas
Meis1 is a member of three-amino-acid loop extension (TALE) homeodomain transcription factors. Studies in the last decade have shown that Meis1 has crucial roles in cardiac regeneration, stem cell function, and tumorigenesis. We have recently demonstrated that knocking out of Meis1 in adult cardiomyocytes resulted in the induction of cardiomyocyte proliferation. This suggests that targeting of Meis1 might be utilized in the manipulation of cardiomyocyte cell cycle post cardiac injuries. In addition, hematopoietic stem cell (HSC) specific deletion of Meis1 leads to in vivo expansion of HSCs pool...
July 24, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28732025/hand-factor-ablation-causes-defective-left-ventricular-chamber-development-and-compromised-adult-cardiac-function
#11
Joshua W Vincentz, Kevin P Toolan, Wenjun Zhang, Anthony B Firulli
Coordinated cardiomyocyte growth, differentiation, and morphogenesis are essential for heart formation. We demonstrate that the bHLH transcription factors Hand1 and Hand2 play critical regulatory roles for left ventricle (LV) cardiomyocyte proliferation and morphogenesis. Using an LV-specific Cre allele (Hand1LV-Cre), we ablate Hand1-lineage cardiomyocytes, revealing that DTA-mediated cardiomyocyte death results in a hypoplastic LV by E10.5. Once Hand1-linage cells are removed from the LV, and Hand1 expression is switched off, embryonic hearts recover by E16...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28729454/multimodal-regulation-of-cardiac-myocyte-proliferation
#12
REVIEW
Xuejun Yuan, Thomas Braun
Efficient cardiac regeneration is closely associated with the ability of cardiac myocytes to proliferate. Fetal or neonatal mouse hearts containing proliferating cardiac myocytes regenerate even extensive injuries, whereas adult hearts containing mostly post-mitotic cardiac myocytes have lost this ability. The same correlation is seen in some homoiotherm species such as teleost fish and urodelian amphibians leading to the hypothesis that cardiac myocyte proliferation is a major driver of heart regeneration...
July 21, 2017: Circulation Research
https://www.readbyqxmd.com/read/28707671/cardiomyocyte-proliferation-remove-brakes-and-push-accelerators
#13
Lingjuan He, Bin Zhou
Adult mammalian hearts cannot repair by themselves after injury due to limited proliferation of cardiomyocytes; removal of cell cycle blocker and/or addition of drugs that boost proliferation of cardiomyocytes provide potential means to cardiac regeneration. Three publications that appeared recently in Nature and Cell Research now provide new hope to the treatment of heart injuries.
August 2017: Cell Research
https://www.readbyqxmd.com/read/28670398/microrna-1825-induces-proliferation-of-adult-cardiomyocytes-and-promotes-cardiac-regeneration-post-ischemic-injury
#14
Raghav Pandey, Sebastian Velasquez, Shazia Durrani, Min Jiang, Michelle Neiman, Jeffrey S Crocker, Joshua B Benoit, Jack Rubinstein, Arghya Paul, Rafeeq Ph Ahmed
In mammals, proliferative capacity of cardiomyocytes is lost soon after birth, while zebrafish and other lower organisms like newts are known to regenerate injured hearts even at an adult age. Here, we show that miR-1825 can induce robust proliferation of adult rat cardiomyocytes and can improve cardiac function in-vivo post myocardial infarction. Rat adult cardiomyocytes transfected with miR-1825 showed a significant increase in DNA synthesis, mitosis, cytokinesis, and an increase in cell number when compared to cel-miR-67 transfected control...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28667270/fam64a-is-a-novel-cell-cycle-promoter-of-hypoxic-fetal-cardiomyocytes-in-mice
#15
Ken Hashimoto, Aya Kodama, Takeshi Honda, Akira Hanashima, Yoshihiro Ujihara, Takashi Murayama, Shin-Ichiro Nishimatsu, Satoshi Mohri
Fetal cardiomyocytes actively proliferate to form the primitive heart in utero in mammals, but they stop dividing shortly after birth. The identification of essential molecules maintaining this active cardiomyocyte proliferation is indispensable for potential adult heart regeneration. A recent study has shown that this proliferation depends on a low fetal oxygen condition before the onset of breathing at birth. We have established an isolation protocol for mouse fetal cardiomyocytes, performed under strict low oxygen conditions to mimic the intrauterine environment, that gives the highest proliferative activities thus far reported...
June 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28659827/increased-postnatal-cardiac-hyperplasia-precedes-cardiomyocyte-hypertrophy-in-a-model-of-hypertrophic-cardiomyopathy
#16
Emily T Farrell, Adrian C Grimes, Willem J de Lange, Annie E Armstrong, J Carter Ralphe
Rationale: Hypertrophic cardiomyopathy (HCM) occurs in ~0.5% of the population and is a leading cause of sudden cardiac death (SCD) in young adults. Cardiomyocyte hypertrophy has been the accepted mechanism for cardiac enlargement in HCM, but the early signaling responsible for initiating hypertrophy is poorly understood. Mutations in cardiac myosin binding protein C (MYBPC3) are among the most common HCM-causing mutations. Ablation of Mybpc3 in an HCM mouse model (cMyBP-C(-/-)) rapidly leads to cardiomegaly by postnatal day (PND) 9, though hearts are indistinguishable from wild-type (WT) at birth...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28659386/fate-predetermination-of-cardiac-myocytes-during-zebrafish-heart-regeneration
#17
Isil Tekeli, Anna Garcia-Puig, Mario Notari, Cristina García-Pastor, Isabelle Aujard, Ludovic Jullien, Angel Raya
Adult zebrafish have the remarkable ability to regenerate their heart upon injury, a process that involves limited dedifferentiation and proliferation of spared cardiomyocytes (CMs), and migration of their progeny. During regeneration, proliferating CMs are detected throughout the myocardium, including areas distant to the injury site, but whether all of them are able to contribute to the regenerated tissue remains unknown. Here, we developed a CM-specific, photoinducible genetic labelling system, and show that CMs labelled in embryonic hearts survive and contribute to all three (primordial, trabecular and cortical) layers of the adult zebrafish heart...
June 2017: Open Biology
https://www.readbyqxmd.com/read/28655642/the-use-and-abuse-of-cre-lox-recombination-to-identify-adult-cardiomyocyte-renewal-rate-and-origin
#18
REVIEW
Iolanda Aquila, Fabiola Marino, Eleonora Cianflone, Pina Marotta, Michele Torella, Vincenzo Mollace, Ciro Indolfi, Bernardo Nadal-Ginard, Daniele Torella
The adult mammalian heart, including the human, is unable to regenerate segmental losses after myocardial infarction. This evidence has been widely and repeatedly used up-to-today to suggest that the myocardium, contrary to most adult tissues, lacks an endogenous stem cell population or more specifically a bona-fide cardiomyocyte-generating progenitor cell of biological significance. In the last 15 years, however, the field has slowly evolved from the dogma that no new cardiomyocytes were produced from shortly after birth to the present consensus that new cardiomyocytes are formed throughout lifespan...
June 24, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28642276/dedifferentiation-proliferation-and-redifferentiation-of-adult-mammalian-cardiomyocytes-after-ischemic-injury
#19
Wei Eric Wang, Liangpeng Li, Xuewei Xia, Wenbin Fu, Qiao Liao, Cong Lan, Dezhong Yang, Hongmei Chen, Rongchuan Yue, Cindy Zeng, Lin Zhou, Bin Zhou, Dayue Darrel Duan, Xiongwen Chen, Steven R Houser, Chunyu Zeng
BACKGROUND: Adult mammalian hearts have a limited ability to generate new cardiomyocytes. Proliferation of existing adult cardiomyocytes (ACMs) is a potential source of new cardiomyocytes. Understanding the fundamental biology of ACM proliferation could be of great clinical significance for treating myocardial infarction (MI). We aim to understand the process and regulation of ACM proliferation and its role in new cardiomyocyte formation of post-MI mouse hearts. METHODS: β-Actin-green fluorescent protein transgenic mice and fate-mapping Myh6-MerCreMer-tdTomato/lacZ mice were used to trace the fate of ACMs...
August 29, 2017: Circulation
https://www.readbyqxmd.com/read/28638481/neonatal-heart-enriched-mir-708-promotes-proliferation-and-stress-resistance-of-cardiomyocytes-in-rodents
#20
Shengqiong Deng, Qian Zhao, Lixiao Zhen, Chuyi Zhang, Cuicui Liu, Guangxue Wang, Lin Zhang, Luer Bao, Ying Lu, Lingyu Meng, Jinhui Lü, Ping Yu, Xin Lin, Yuzhen Zhang, Yi-Han Chen, Huimin Fan, William C Cho, Zhongmin Liu, Zuoren Yu
Adult heart has limited potential for regeneration after pathological injury due to the limited cell proliferation of cardiomyocytes and the quiescent status of progenitor cells. As such, induction of cell-cycle reentry of cardiomyocytes is one of the key strategies for regeneration of damaged heart. In this study, a subset of miRNAs including miR-708 were identified to be much more abundant in the embryonic and neonatal cardiomyocytes than that in adult rodents. Overexpression of miR-708 promoted cellular proliferation of H9C2 cells or primary cardiomyocytes from neonatal rats or mice in vitro...
2017: Theranostics
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