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adult cardiomyocyte proliferation

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https://www.readbyqxmd.com/read/28629520/the-erythropoietin-system-protects-the-heart-upon-injury-by-cardiac-progenitor-cell-activation
#1
Maria P Zafeiriou
Erythropoietin (EPO) is a growth hormone, widely known for its role in erythropoiesis. The broad expression of erythropoietin receptor (EPOR) in adult organs suggested that EPO may also affect other cells besides late erythroid progenitors. In the embryonic heart, EPOR is expressed in all cells including the immature proliferating cardiomyocytes. In contrast to the embryonic heart in adulthood, EPOR expression is decreased and mainly detected in immature proliferating cells (i.e., resident cardiac progenitor cells) rather than in terminally differentiated cells (i...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28621328/live-cell-screening-platform-identifies-ppar%C3%AE-as-a-regulator-of-cardiomyocyte-proliferation-and-cardiac-repair
#2
Ajit Magadum, Yishu Ding, Lan He, Teayoun Kim, Mohankrishna Dalvoy Vasudevarao, Qinqiang Long, Kevin Yang, Nadeera Wickramasinghe, Harsha V Renikunta, Nicole Dubois, Gilbert Weidinger, Qinglin Yang, Felix B Engel
Zebrafish can efficiently regenerate their heart through cardiomyocyte proliferation. In contrast, mammalian cardiomyocytes stop proliferating shortly after birth, limiting the regenerative capacity of the postnatal mammalian heart. Therefore, if the endogenous potential of postnatal cardiomyocyte proliferation could be enhanced, it could offer a promising future therapy for heart failure patients. Here, we set out to systematically identify small molecules triggering postnatal cardiomyocyte proliferation. By screening chemical compound libraries utilizing a Fucci-based system for assessing cell cycle stages, we identified carbacyclin as an inducer of postnatal cardiomyocyte proliferation...
June 16, 2017: Cell Research
https://www.readbyqxmd.com/read/28617969/conditionally-targeted-deletion-of-psen1-leads-to-diastolic-heart-dysfunction
#3
Xiao-Wei Song, Qing-Ning Yuan, Ying Tang, Mi Cao, Ya-Feng Shen, Zhen-Yu Zeng, Chang-Hai Lei, SongHua Li, Xian-Xian Zhao, Yong-Ji Yang
Recently, PSEN1 has been reported to have mutations in dilated cardiomyopathy pedigrees. However, the function and mechanism of PSEN1 in cardiomyopathy remains unresolved. Here, we established 4 types of genetically modified mice to determine the function of PSEN1 in cardiac development and pathology. PSEN1 null mutation resulted in perinatal death, retardation of heart growth, ventricular dilatation, septum defects, and valvular thickening. PSEN1 knockout in adults led to decreased muscle fibers, widened sarcomere Z lines and reduced lengths of sarcomeres in cardiomyocytes...
June 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28581498/dystrophin-glycoprotein-complex-sequesters-yap-to-inhibit-cardiomyocyte-proliferation
#4
Yuka Morikawa, Todd Heallen, John Leach, Yang Xiao, James F Martin
The regenerative capacity of the adult mammalian heart is limited because of the reduced ability of cardiomyocytes (CMs) to progress through mitosis(1). The regenerative capacity of endogenous CMs exists at birth but is lost postnatally, with subsequent organ growth occurring through CM hypertrophy(2,3). The Hippo pathway, a conserved kinase cascade, inhibits CM proliferation in the developing heart to control heart size and in the adult heart to prevent regeneration(4,5). The dystrophin glycoprotein complex (DGC), a multicomponent transmembrane complex linking the actin cytoskeleton to extracellular matrix, is essential for CM homeostasis...
June 5, 2017: Nature
https://www.readbyqxmd.com/read/28581497/the-extracellular-matrix-protein-agrin-promotes-heart-regeneration-in-mice
#5
Elad Bassat, Yara Eid Mutlak, Alex Genzelinakh, Ilya Y Shadrin, Kfir Baruch-Umansky, Oren Yifa, David Kain, Dana Rajchman, John Leach, Daria Riabov Bassat, Yael Udi, Rachel Sarig, Irit Sagi, James F Martin, Nenad Bursac, Shenhav Cohen, Eldad Tzahor
The adult mammalian heart is non-regenerative due to the post-mitotic nature of cardiomyocytes. The neonatal mouse heart can regenerate, but only for the first week of life. Here we show that changes in the composition of the extracellular matrix (ECM) during this week can affect cardiomyocyte growth and differentiation in mice. We identify Agrin, a component of neonatal ECM, as required for the full regenerative capacity of neonatal mouse hearts. In vitro, recombinant Agrin promotes the division of mouse and human iPSC-derived cardiomyocytes via a mechanism that involves the disassembly of the dystrophin glycoprotein complex and Yap and ERK-mediated signaling...
June 5, 2017: Nature
https://www.readbyqxmd.com/read/28578380/the-zebrafish-ventricle-a-hub-of-cardiac-endothelial-cells-for-in-vitro-cell-behavior-studies
#6
Chinmoy Patra, Zacharias Kontarakis, Harmandeep Kaur, Amey Rayrikar, Debanjan Mukherjee, Didier Y R Stainier
Despite our increasing understanding of zebrafish heart development and regeneration, there is limited information about the distribution of endothelial cells (ECs) in the adult zebrafish heart. Here, we investigate and compare the distribution of cardiac ECs (cECs) in adult mouse and zebrafish ventricles. Surprisingly, we find that (i) active coronary vessel growth is present in adult zebrafish, (ii) ~37 and ~39% of cells in the zebrafish heart are ECs and cardiomyocytes, respectively, a composition similar to that seen in mouse...
June 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28523343/hh-signaling-in-regeneration-of-the-ischemic-heart
#7
REVIEW
Marina Dunaeva, Johannes Waltenberger
Myocardial infarction (MI) is caused by the occlusion of a coronary artery due to underlying atherosclerosis complicated by localized thrombosis. The blockage of blood flow leads to cardiomyocyte (CM) death in the infarcted area. Adult mammalian cardiomyocytes have little capacity to proliferate in response to injury; however, some pathways active during embryogenesis and silent during adult life are recruited in response to tissue injury. One such example is hedgehog (Hh) signaling. Hh is involved in the embryonic development of the heart and coronary vascular system...
May 18, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28469272/adult-murine-cardiomyocytes-exhibit-regenerative-activity-with-cell-cycle-reentry-through-stat3-in-the-healing-process-of-myocarditis
#8
Akimitsu Miyawaki, Masanori Obana, Yusuke Mitsuhara, Aya Orimoto, Yusuke Nakayasu, Tomomi Yamashita, So-Ichiro Fukada, Makiko Maeda, Hiroyuki Nakayama, Yasushi Fujio
Mammalian cardiomyocytes substantially lose proliferative capacity immediately after birth, limiting adult heart regeneration after injury. However, clinical myocarditis appears to be self-limiting with tissue-reparative properties. Here, we investigated the molecular mechanisms underlying the recovery from myocarditis with regard to cardiomyocyte proliferation using an experimental autoimmune myocarditis (EAM) model. Three weeks after EAM induction (EAM3w), cardiac tissue displayed infiltration of inflammatory cells with cardiomyocyte apoptosis...
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28464412/heart-specific-expression-of-laminopathic-mutations-in-transgenic-zebrafish
#9
Ajay D Verma, Veena K Parnaik
Lamins are key determinants of nuclear organization and function in the metazoan nucleus. Mutations in human lamin A cause a spectrum of genetic diseases that affect cardiac muscle and skeletal muscle as well as other tissues. A few laminopathies have been modeled using the mouse. As zebrafish is a well established model for the study of cardiac development and disease, we have investigated the effects of heart-specific lamin A mutations in transgenic zebrafish. We have developed transgenic lines of zebrafish expressing conserved lamin A mutations that cause cardiac dysfunction in humans...
May 2, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28459713/cardiac-outcomes-after-perinatal-sertraline-exposure-in-mice
#10
Sarah E Haskell, Cecilia Lo, Mitchell E Kent, Timothy M Eggleston, Kenneth A Volk, Benjamin E Reinking, Robert D Roghair
Selective serotonin reuptake inhibitors are prescribed to 6-10% of pregnant women in the United States. Using an intrauterine plus neonatal exposure model to represent exposure throughout human pregnancy, we hypothesized sertraline exposure would impact intracardiac serotonin signaling and lead to small left heart syndrome in the absence of maternal psychopathology. C57BL/6 adult female mice received sertraline (5 mg/kg/d IP) or saline throughout pregnancy to time of delivery. Pups maintained exposure on postnatal days 1-14 to encompass the developmental window analogous to human gestation...
April 25, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28455218/age-dependent-functional-crosstalk-between-cardiac-fibroblasts-and-cardiomyocytes-in-a-3d-engineered-cardiac-tissue
#11
Yanzhen Li, Huda Asfour, Nenad Bursac
Complex heterocellular interactions between cardiomyocytes and fibroblasts in the heart involve their bidirectional signaling via cell-cell contacts, paracrine factors, and extracellular matrix (ECM). These interactions vary with heart development and pathology leading to changes in cardiac structure and function. Whether cardiac fibroblasts of different ages interact differentially with cardiomyocytes to distinctly impact their function remains unknown. Here, we explored the direct structural and functional effects of fetal and adult cardiac fibroblasts on cardiomyocytes using a tissue-engineered 3D co-culture system...
April 25, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28378126/global-transcriptomic-analysis-of-induced-cardiomyocytes-predicts-novel-regulators-for-direct-cardiac-reprogramming
#12
Mahmood Talkhabi, Seyed Morteza Razavi, Ali Salari
Heart diseases are the most significant cause of morbidity and mortality in the world. De novo generated cardiomyocytes (CMs) are a great cellular source for cell-based therapy and other potential applications. Direct cardiac reprogramming is the newest method to produce CMs, known as induced cardiomyocytes (iCMs). During a direct cardiac reprogramming, also known as transdifferentiation, non-cardiac differentiated adult cells are reprogrammed to cardiac identity by forced expression of cardiac-specific transcription factors (TFs) or microRNAs...
June 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28323876/pim1-minicircle-as-a-therapeutic-treatment-for-myocardial-infarction
#13
Nan Liu, Bingyan J Wang, Kathleen M Broughton, Roberto Alvarez, Sailay Siddiqi, Rebeca Loaiza, Nicky Nguyen, Pearl Quijada, Natalie Gude, Mark A Sussman
PIM1, a pro-survival gene encoding a serine/ threonine kinase, influences cell proliferation and survival. Modification of cardiac progenitor cells (CPCs) or cardiomyocytes with PIM1 using a lentivirus-based delivery method showed long-term improved cardiac function after myocardial infarction (MI). However, lentivirus based delivery methods have stringent FDA regulation with respect to clinical trials. To provide an alternative and low risk PIM1 delivery method, this study examined the use of a non-viral modified plasmid-minicircle (MC) as a vehicle to deliver PIM1 into mouse CPCs (mCPCs) in vitro and the myocardium in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28304151/cardiac-cell-proliferation-is-not-necessary-for-exercise-induced-cardiac-growth-but-required-for-its-protection-against-ischaemia-reperfusion-injury
#14
Yihua Bei, Siyi Fu, Xiangming Chen, Mei Chen, Qiulian Zhou, Pujiao Yu, Jianhua Yao, Hongbao Wang, Lin Che, Jiahong Xu, Junjie Xiao
The adult heart retains a limited ability to regenerate in response to injury. Although exercise can reduce cardiac ischaemia/reperfusion (I/R) injury, the relative contribution of cardiac cell proliferation including newly formed cardiomyocytes remains unclear. A 4-week swimming murine model was utilized to induce cardiac physiological growth. Simultaneously, the antineoplastic agent 5-fluorouracil (5-FU), which acts during the S phase of the cell cycle, was given to mice via intraperitoneal injections. Using EdU and Ki-67 immunolabelling, we showed that exercise-induced cardiac cell proliferation was blunted by 5-FU...
March 17, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28280861/a-growing-role-for-the-hippo-signaling-pathway-in-the-heart
#15
REVIEW
Yu Zhang, Dominic P Del Re
Heart disease is a major cause of clinical morbidity and mortality, and a significant health and economic burden worldwide. The loss of functional cardiomyocytes, often a result of myocardial infarction, leads to impaired cardiac output and ultimately heart failure. Therefore, efforts to improve cardiomyocyte viability and stimulate cardiomyocyte proliferation remain attractive therapeutic goals. Originally identified in Drosophila, the Hippo signaling pathway is highly conserved from flies to humans and regulates organ size through modulation of both cell survival and proliferation...
May 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28278282/persistent-fibrosis-hypertrophy-and-sarcomere-disorganisation-after-endoscopy-guided-heart-resection-in-adult-xenopus
#16
Lindsey Marshall, Céline Vivien, Fabrice Girardot, Louise Péricard, Barbara A Demeneix, Laurent Coen, Norin Chai
Models of cardiac repair are needed to understand mechanisms underlying failure to regenerate in human cardiac tissue. Such studies are currently dominated by the use of zebrafish and mice. Remarkably, it is between these two evolutionary separated species that the adult cardiac regenerative capacity is thought to be lost, but causes of this difference remain largely unknown. Amphibians, evolutionary positioned between these two models, are of particular interest to help fill this lack of knowledge. We thus developed an endoscopy-based resection method to explore the consequences of cardiac injury in adult Xenopus laevis...
2017: PloS One
https://www.readbyqxmd.com/read/28277146/efficacy-of-gold-nanoparticles-against-isoproterenol-induced-acute-myocardial-infarction-in-adult-male-albino-rats
#17
Samah M Ahmed, Shaimaa Ali Abdelrahman, Alaa Elsayed Salama
This study was undertaken to investigate the role of gold nanoparticles (GNPs) of 50 nm diameter on isoproterenol (ISO) induced acute myocardial infarction in adult male albino rats. Forty five adult Wistar male albino rats were equally divided into three groups. Control (group I) was further subdivided into three subgroups. In group II, the rats received ISO subcutaneously at a dose of 100 mg/kg for three days. In group III, rats received ISO as group II and then GNPs (400 μg/kg/day) intravenously for 14 consecutive days...
March 2017: Ultrastructural Pathology
https://www.readbyqxmd.com/read/28185170/mechanisms-of-cardiomyocyte-proliferation-and-differentiation-in-development-and-regeneration
#18
REVIEW
Jessie Wettig Yester, Bernhard Kühn
PURPOSE OF REVIEW: Congenital heart disease is the most common birth defect and acquired heart disease is the leading cause of death in adults. Understanding the mechanisms that drive cardiomyocyte proliferation and differentiation has the potential to advance the understanding and potentially the treatment of different cardiac pathologies, ranging from myopathies and heart failure to myocardial infarction. This review focuses on studies aimed at elucidating signal transduction pathways and molecular mechanisms that promote proliferation, differentiation, and regeneration of differentiated heart muscle cells, cardiomyocytes...
February 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28174241/development-of-a-human-cardiac-organoid-injury-model-reveals-innate-regenerative-potential
#19
Holly K Voges, Richard J Mills, David A Elliott, Robert G Parton, Enzo R Porrello, James E Hudson
The adult human heart possesses a limited regenerative potential following an ischemic event, and undergoes a number of pathological changes in response to injury. While cardiac regeneration has been documented in zebrafish and neonatal mouse hearts, it is currently unknown whether the immature human heart is capable of undergoing complete regeneration. Combined progress in pluripotent stem cell differentiation and tissue engineering has facilitated the development of human cardiac organoids (hCO), which resemble fetal heart tissue and can be used to address this important knowledge gap...
February 7, 2017: Development
https://www.readbyqxmd.com/read/28170287/intermediate-reprogramming-of-mouse-skin-fibroblasts-into-stem-like-cells-by-bone-morphogenetic-protein-4
#20
Seung-Eun Lee, Sang-Jun Uhm, Yeo-Jin Son, Yun-Gwi Park, Eun-Young Kim, Se-Pill Park
Specific transcription factors are sufficient to reprogram fully induced pluripotent stem cells or other types of cells. These findings raise the question of whether chemical molecules or proteins can replace transcription factors to alter the defined cell fate. In this study, we treated mouse skin fibroblasts (MSFs) with bone morphogenetic protein 4 (BMP4) and examined intermediate reprogramming of MSFs into stem-like cells. Putative epidermal stem cells isolated from the ventral skin epidermis of an adult mouse were used to confirm the reprogramming activity of BMP4, which increased the proliferation of these cells...
April 2017: Cellular Reprogramming
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