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adult cardiomyocyte proliferation

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https://www.readbyqxmd.com/read/29142194/transient-cardiomyocyte-fusion-regulates-cardiac-development-in-zebrafish
#1
Suphansa Sawamiphak, Zacharias Kontarakis, Alessandro Filosa, Sven Reischauer, Didier Y R Stainier
Cells can sacrifice their individuality by fusing, but the prevalence and significance of this process are poorly understood. To approach these questions, here we generate transgenic reporter lines in zebrafish to label and specifically ablate fused cells. In addition to skeletal muscle cells, the reporters label cardiomyocytes starting at an early developmental stage. Genetic mosaics generated by cell transplantation show cardiomyocytes expressing both donor- and host-derived transgenes, confirming the occurrence of fusion in larval hearts...
November 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29067089/is-biological-repair-of-heart-on-the-horizon
#2
REVIEW
H R Ahmad, Satwat Hashmi
The stem cells keep us young by endogenously repairing us upon need. They do so bysmartly one step forward towards differentiation while another step backward to nurturethe undifferentiated stem cells. They are building blocks for every organ witha differential rate of repair of worn out tissues. Since stem cells can be cultured with a normal karyo type, they could be the ideal source for heart repair after myocardial infarction. As opposed to lower vertebrates and neonatal mice, cardiac regeneration in adult mammalian heart seems to be difficult to assess with a solid evidence of cytokinesis...
July 2017: Pakistan Journal of Medical Sciences Quarterly
https://www.readbyqxmd.com/read/28985522/mononuclear-diploidy-at-the-heart-of-cardiomyocyte-proliferation
#3
Paula A da Costa Martins
Reporting in Nature Genetics, Patterson et al. (2017) show that adult mammalian hearts possess an innate capacity to regenerate, which depends on a small population of mononuclear diploid cardiomyocytes. These cells undergo karyokinesis and cytokinesis, raising the possibility that endogenous cardiac muscle cells can be stimulated to proliferate for myocardial repair.
October 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28976966/hippo-pathway-deficiency-reverses-systolic-heart-failure-after-infarction
#4
John P Leach, Todd Heallen, Min Zhang, Mahdis Rahmani, Yuka Morikawa, Matthew C Hill, Ana Segura, James T Willerson, James F Martin
Mammalian organs vary widely in regenerative capacity. Poorly regenerative organs, such as the heart are particularly vulnerable to organ failure. Once established, heart failure commonly results in mortality. The Hippo pathway, a kinase cascade that prevents adult cardiomyocyte proliferation and regeneration, is upregulated in human heart failure. Here we show that deletion of the Hippo pathway component Salvador (Salv) in mouse hearts with established ischaemic heart failure after myocardial infarction induces a reparative genetic program with increased scar border vascularity, reduced fibrosis, and recovery of pumping function compared with controls...
October 12, 2017: Nature
https://www.readbyqxmd.com/read/28948298/microrna-210-mediated-proliferation-survival-and-angiogenesis-promote-cardiac-repair-post-myocardial-infarction-in-rodents
#5
Mohammed Arif, Raghav Pandey, Perwez Alam, Shujia Jiang, Sakthivel Sadayappan, Arghya Paul, Rafeeq P H Ahmed
An innovative approach for cardiac regeneration following injury is to induce endogenous cardiomyocyte (CM) cell cycle re-entry. In the present study, CMs from adult rat hearts were isolated and transfected with cel-miR-67 (control) and rno-miR-210. A significant increase in CM proliferation and mono-nucleation were observed in miR-210 group, in addition to a reduction in CM size, multi-nucleation, and cell death. When compared to control, β-catenin and Bcl-2 were upregulated while APC (adenomatous polyposis coli), p16, and caspase-3 were downregulated in miR-210 group...
December 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28916735/functional-screening-in-human-cardiac-organoids-reveals-a-metabolic-mechanism-for-cardiomyocyte-cell-cycle-arrest
#6
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)...
October 3, 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
#7
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 20, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28895052/the-effects-of-periostin-in-a-rat-model-of-isoproterenol-mediated-cardiotoxicity
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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