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Cardiomyocyte renewal

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https://www.readbyqxmd.com/read/28684531/cardiomyocyte-regeneration-a-consensus-statement
#1
Thomas Eschenhagen, Roberto Bolli, Thomas Braun, Loren J Field, Bernd K Fleischmann, Jonas Frisén, Mauro Giacca, Joshua M Hare, Steven R Houser, Richard T Lee, Eduardo Marbán, James F Martin, Jeffery D Molkentin, Charles E Murry, Paul R Riley, Pilar Ruiz-Lozano, Hesham A Sadek, Mark A Sussman, Joseph A Hill
Cell therapy is an exciting option for repairing the injured heart, one which has attracted considerable interest over the past 15 years. Consensus exists that the injection/infusion or tissue-based implantation of various cell types may exert therapeutic effects, and there is general agreement that additional molecular, translational and clinical studies are required to define the optimal cell source, method of delivery, and underlying mechanism(s) of action.One of the remaining questions in this field pertains to cardiomyocyte turnover under normal and diseased conditions and its contribution to the beneficial effects of cell therapy...
July 6, 2017: Circulation
https://www.readbyqxmd.com/read/28655642/the-use-and-abuse-of-cre-lox-recombination-to-identify-adult-cardiomyocyte-renewal-rate-and-origin
#2
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/28649106/-aging-and-homeostasis-aging-control-through-cardiac-regenerative-medicine
#3
Katsuhisa Matsuura
Heart disease is one of the leading causes of death in the developed countries and various physical conditions in heart failure attribute to the impaired physical activities, which promotes aging. The principle cause of heart failure is the loss of self-renewal ability of cardiomyocytes in various injuries such as myocardial infarction. The replacement of injured tissues with the regenerated human myocardial tissues using technologies on tissue engineering and iPS cell will provide us the novel therapeutic strategy for heart failure and the related aging issues...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28537559/enforcement-of-developmental-lineage-specificity-by-transcription-factor-oct1
#4
Zuolian Shen, Jinsuk Kang, Arvind Shakya, Marcin Tabaka, Elke A Jarboe, Aviv Regev, Dean Tantin
Embryonic stem cells co-express Oct4 and Oct1, a related protein with similar DNA-binding specificity. To study the role of Oct1 in ESC pluripotency and transcriptional control, we constructed germline and inducible-conditional Oct1-deficient ESC lines. ESCs lacking Oct1 show normal appearance, self-renewal and growth but manifest defects upon differentiation. They fail to form beating cardiomyocytes, generate neurons poorly, form small, poorly differentiated teratomas, and cannot generate chimeric mice. Upon RA-mediated differentiation, Oct1-deficient cells induce lineage-appropriate developmentally poised genes poorly while lineage-inappropriate genes, including extra-embryonic genes, are aberrantly expressed...
May 24, 2017: ELife
https://www.readbyqxmd.com/read/28229406/manipulating-the-proliferative-potential-of-cardiomyocytes-by-gene-transfer
#5
Giulia Prosdocimo, Mauro Giacca
In contrast to prenatal life, cardiomyocyte proliferation in mammals is rapidly blunted after birth; as a consequence, clinically significant cardiac regeneration does not occur in adulthood. Thus, the modulation of cardiomyocyte proliferation by gene transfer offers an invaluable opportunity to both understand the mechanisms regulating renewal of these cells in the fetus and identify novel strategies for myocardial repair.In this Chapter, we report an exhaustive protocol to isolate, culture, and manipulate the properties of neonatal ventricular rat cardiomyocytes by small RNA transfection or transduction with viral vectors based on the adeno-associated virus, which exhibit exquisite tropism for these cells...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28223222/disrupting-the-key-circadian-regulator-clock-leads-to-age-dependent-cardiovascular-disease
#6
Faisal J Alibhai, Jonathan LaMarre, Cristine J Reitz, Elena V Tsimakouridze, Jeffrey T Kroetsch, Steffen-Sebastian Bolz, Alex Shulman, Samantha Steinberg, Thomas P Burris, Gavin Y Oudit, Tami A Martino
The circadian mechanism underlies daily rhythms in cardiovascular physiology and rhythm disruption is a major risk factor for heart disease and worse outcomes. However, the role of circadian rhythms is generally clinically unappreciated. Clock is a core component of the circadian mechanism and here we examine the role of Clock as a vital determinant of cardiac physiology and pathophysiology in aging. Clock(Δ19/Δ19) mice develop age-dependent increases in heart weight, hypertrophy, dilation, impaired contractility, and reduced myogenic responsiveness...
April 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28104772/the-elusive-progenitor-cell-in-cardiac-regeneration-slip-slidin-away
#7
REVIEW
Chen-Leng Cai, Jeffery D Molkentin
The adult human heart is unable to regenerate after various forms of injury, suggesting that this organ lacks a biologically meaningful endogenous stem cell pool. However, injecting the infarcted area of the adult mammalian heart with exogenously prepared progenitor cells of various types has been reported to create new myocardium by the direct conversion of these progenitor cells into cardiomyocytes. These reports remain controversial because follow-up studies from independent laboratories failed to observe such an effect...
January 20, 2017: Circulation Research
https://www.readbyqxmd.com/read/28074006/autocrine-wnt-regulates-the-survival-and-genomic-stability-of-embryonic-stem-cells
#8
Iris Augustin, Dyah L Dewi, Jennifer Hundshammer, Gerrit Erdmann, Grainne Kerr, Michael Boutros
Wnt signaling plays an important role in the self-renewal and differentiation of stem cells. The secretion of Wnt ligands requires Evi (also known as Wls). Genetically ablating Evi provides an experimental approach to studying the consequence of depleting all redundant Wnt proteins, and overexpressing Evi enables a nonspecific means of increasing Wnt signaling. We generated Evi-deficient and Evi-overexpressing mouse embryonic stem cells (ESCs) to analyze the role of autocrine Wnt production in self-renewal and differentiation...
January 10, 2017: Science Signaling
https://www.readbyqxmd.com/read/28066829/the-multifaceted-role-of-nrf2-in-mitochondrial-function
#9
REVIEW
Kira M Holmström, Rumen V Kostov, Albena T Dinkova-Kostova
The transcription factor nuclear factor erythroid 2 p45-related factor 2 (Nrf2) is the master regulator of the cellular redox homeostasis. Nrf2 target genes comprise of a large network of antioxidant enzymes, proteins involved in xenobiotic detoxification, repair and removal of damaged proteins, inhibition of inflammation, as well as other transcription factors. In recent years it has emerged that as part of its role as a regulator of cytoprotective gene expression, Nrf2 impacts mitochondrial function. Increased Nrf2 activity defends against mitochondrial toxins...
December 2016: Current Opinion in Toxicology
https://www.readbyqxmd.com/read/28063988/engineered-extracellular-microenvironment-with-a-tunable-mechanical-property-for-controlling-cell-behavior-and-cardiomyogenic-fate-of-cardiac-stem-cells
#10
Min-Young Choi, Jong-Tae Kim, Won-Jin Lee, Yunki Lee, Kyung Min Park, Young-Il Yang, Ki Dong Park
Endogenous cardiac stem cells (CSCs) are known to play a certain role in the myocardial homeostasis of the adult heart. The extracellular matrix (ECM) surrounding CSCs provides mechanical signals to regulate a variety of cell behaviors, yet the impact in the adult heart of these mechanical properties of ECM on CSC renewal and fate decisions is mostly unknown. To elucidate CSC mechanoresponses at the individual cell and myocardial level, we used the sol-to-gel transitional gelatin-poly(ethylene glycol)-tyramine (GPT) hydrogel with a tunable mechanical property to construct a three-dimensional (3D) matrix for culturing native myocardium and CSCs...
January 4, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/27934662/cardiomyocyte-specific-expression-of-the-nuclear-matrix-protein-ciz1-stimulates-production-of-mono-nucleated-cells-with-an-extended-window-of-proliferation-in-the-postnatal-mouse-heart
#11
Sumia A Bageghni, Georgia A Frentzou, Mark J Drinkhill, William Mansfield, Dawn Coverley, Justin F X Ainscough
Myocardial injury in mammals leads to heart failure through pathological cardiac remodelling that includes hypertrophy, fibrosis and ventricular dilatation. Central to this is inability of the mammalian cardiomyocyte to self-renew due to entering a quiescent state after birth. Modulation of the cardiomyocyte cell-cycle after injury is therefore a target mechanism to limit damage and potentiate repair and regeneration. Here, we show that cardiomyocyte-specific over-expression of the nuclear-matrix--associated DNA replication protein, CIZ1, extends their window of proliferation during cardiac development, delaying onset of terminal differentiation without compromising function...
January 15, 2017: Biology Open
https://www.readbyqxmd.com/read/27927803/dating-the-heart-exploring-cardiomyocyte-renewal-in-humans
#12
REVIEW
Evan Graham, Olaf Bergmann
Regenerative mechanisms reported in the hearts of lower vertebrates have been recapitulated in the mammalian milieu, and recent studies have provided strong evidence for cardiomyocyte turnover in humans. These findings speak to an emerging consensus that adult mammalian cardiomyocytes do have the ability to divide, and it stands to reason that enrichment of this innate proliferative capacity should prove essential for complete cardiac regeneration.
January 2017: Physiology
https://www.readbyqxmd.com/read/27799944/repair-injured-heart-by-regulating-cardiac-regenerative-signals
#13
REVIEW
Wen-Feng Cai, Guan-Sheng Liu, Lei Wang, Christian Paul, Zhi-Li Wen, Yigang Wang
Cardiac regeneration is a homeostatic cardiogenic process by which the sections of malfunctioning adult cardiovascular tissues are repaired and renewed employing a combination of both cardiomyogenesis and angiogenesis. Unfortunately, while high-quality regeneration can be performed in amphibians and zebrafish hearts, mammalian hearts do not respond in kind. Indeed, a long-term loss of proliferative capacity in mammalian adult cardiomyocytes in combination with dysregulated induction of tissue fibrosis impairs mammalian endogenous heart regenerative capacity, leading to deleterious cardiac remodeling at the end stage of heart failure...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27798600/hypoxia-induces-heart-regeneration-in-adult-mice
#14
Yuji Nakada, Diana C Canseco, SuWannee Thet, Salim Abdisalaam, Aroumougame Asaithamby, Celio X Santos, Ajay M Shah, Hua Zhang, James E Faber, Michael T Kinter, Luke I Szweda, Chao Xing, Zeping Hu, Ralph J Deberardinis, Gabriele Schiattarella, Joseph A Hill, Orhan Oz, Zhigang Lu, Cheng Cheng Zhang, Wataru Kimura, Hesham A Sadek
The adult mammalian heart is incapable of regeneration following cardiomyocyte loss, which underpins the lasting and severe effects of cardiomyopathy. Recently, it has become clear that the mammalian heart is not a post-mitotic organ. For example, the neonatal heart is capable of regenerating lost myocardium, and the adult heart is capable of modest self-renewal. In both of these scenarios, cardiomyocyte renewal occurs via the proliferation of pre-existing cardiomyocytes, and is regulated by aerobic-respiration-mediated oxidative DNA damage...
January 12, 2017: Nature
https://www.readbyqxmd.com/read/27790620/immune-modulation-of-cardiac-repair-and-regeneration-the-art-of-mending-broken-hearts
#15
REVIEW
Ivana Zlatanova, Cristina Pinto, Jean-Sébastien Silvestre
The accumulation of immune cells is among the earliest responses that manifest in the cardiac tissue after injury. Both innate and adaptive immunity coordinate distinct and mutually non-exclusive events governing cardiac repair, including elimination of the cellular debris, compensatory growth of the remaining cardiac tissue, activation of resident or circulating precursor cells, quantitative and qualitative modifications of the vascular network, and formation of a fibrotic scar. The present review summarizes the mounting evidence suggesting that the inflammatory response also guides the regenerative process following cardiac damage...
2016: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/27679798/the-role-of-cardiac-side-population-cells-in-cardiac-regeneration
#16
REVIEW
Amritha Yellamilli, Jop H van Berlo
The heart has a limited ability to regenerate. It is important to identify therapeutic strategies that enhance cardiac regeneration in order to replace cardiomyocytes lost during the progression of heart failure. Cardiac progenitor cells are interesting targets for new regenerative therapies because they are self-renewing, multipotent cells located in the heart. Cardiac side population cells (cSPCs), the first cardiac progenitor cells identified in the adult heart, have the ability to differentiate into cardiomyocytes, endothelial cells, smooth muscle cells, and fibroblasts...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27635079/is-stimulation-of-cardiomyocyte-renewal-a-facette-of-reversible-catecholamine-toxicity
#17
EDITORIAL
Thomas Eschenhagen
No abstract text is available yet for this article.
September 16, 2016: Circulation Research
https://www.readbyqxmd.com/read/27575008/gsk-3%C3%AE-inhibitor-chir-99021-promotes-proliferation-through-upregulating-%C3%AE-catenin-in-neonatal-atrial-human-cardiomyocytes
#18
Shoubao Wang, Lincai Ye, Minghui Li, Jinfen Liu, Chuan Jiang, Haifa Hong, Hongbin Zhu, Yanjun Sun
BACKGROUND: The renewal capacity of neonate human cardiomyocytes provides an opportunity to manipulate endogenous cardiogenic mechanisms for supplementing the loss of cardiomyocytes caused by myocardial infarction or other cardiac diseases. GSK-3β inhibitors have been recently shown to promote cardiomyocyte proliferation in rats and mice, thus may be ideal candidates for inducing human cardiomyocyte proliferation. METHODS: Human cardiomyocytes were isolated from right atrial specimens obtained during routine surgery for ventricle septal defect and cultured with either GSK-3β inhibitor (CHIR-99021) or β-catenin inhibitor (IWR-1)...
December 2016: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/27498864/erk5-is-a-key-regulator-of-naive-primed-transition-and-embryonic-stem-cell-identity
#19
Charles A C Williams, Rosalia Fernandez-Alonso, Jinhua Wang, Rachel Toth, Nathanael S Gray, Greg M Findlay
Embryonic stem cells (ESCs) can self-renew or differentiate into any cell type, a phenomenon known as pluripotency. Distinct pluripotent states, termed naive and primed pluripotency, have been described. However, the mechanisms that control naive-primed pluripotent transition are poorly understood. Here, we perform a targeted screen for kinase inhibitors, which modulate the naive-primed pluripotent transition. We find that XMD compounds, which selectively inhibit Erk5 kinase and BET bromodomain family proteins, drive ESCs toward primed pluripotency...
August 16, 2016: Cell Reports
https://www.readbyqxmd.com/read/27472922/bmi1-cardiac-progenitor-cells-contribute-to-myocardial-repair-following-acute-injury
#20
Iñigo Valiente-Alandi, Carmen Albo-Castellanos, Diego Herrero, Iria Sanchez, Antonio Bernad
BACKGROUND: The inability of the adult mammalian heart to replace cells lost after severe cardiac injury compromises organ function. Although the heart is one of the least regenerative organs in the body, evidence accumulated in recent decades indicates a certain degree of renewal after injury. We have evaluated the role of cardiac Bmi1 (+) progenitor cells (Bmi1-CPC) following acute myocardial infarction (AMI). METHODS: Bmi1 (Cre/+);Rosa26 (YFP/+) (Bmi1-YFP) mice were used for lineage tracing strategy...
July 30, 2016: Stem Cell Research & Therapy
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