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Turnover of cardiomyocytes

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https://www.readbyqxmd.com/read/27881552/cardiac-t-tubule-microanatomy-and-function
#1
REVIEW
TingTing Hong, Robin M Shaw
Unique to striated muscle cells, transverse tubules (t-tubules) are membrane organelles that consist of sarcolemma penetrating into the myocyte interior, forming a highly branched and interconnected network. Mature t-tubule networks are found in mammalian ventricular cardiomyocytes, with the transverse components of t-tubules occurring near sarcomeric z-discs. Cardiac t-tubules contain membrane microdomains enriched with ion channels and signaling molecules. The microdomains serve as key signaling hubs in regulation of cardiomyocyte function...
January 2017: Physiological Reviews
https://www.readbyqxmd.com/read/27872447/evolving-approaches-to-heart-regeneration-by-therapeutic-stimulation-of-resident-cardiomyocyte-cell-cycle
#2
Raife Dilek Turan, Galip Servet Aslan, Doğacan Yücel, Remziye Döğer, Fatih Kocabaş
Heart has long been considered a terminally differentiated organ. Recent studies, however, have suggested that there is a modest degree of cardiomyocyte (CM) turnover in adult mammalian heart, albeit not sufficient for replacement of lost CMs following cardiac injuries. Cardiac regeneration studies in various model organisms including zebrafish, newt, and more recently in neonatal mouse, have demonstrated that CM dedifferentiation and concomitant proliferation play important roles in replacement of lost CMs and restoration of cardiac contractility...
November 2016: Anatolian Journal of Cardiology
https://www.readbyqxmd.com/read/27743117/stiff-matrix-induces-switch-to-pure-%C3%AE-cardiac-myosin-heavy-chain-expression-in-human-esc-derived-cardiomyocytes
#3
Natalie Weber, Kristin Schwanke, Stephan Greten, Meike Wendland, Bogdan Iorga, Martin Fischer, Cornelia Geers-Knörr, Jan Hegermann, Christoph Wrede, Jan Fiedler, Henning Kempf, Annika Franke, Birgit Piep, Angelika Pfanne, Thomas Thum, Ulrich Martin, Bernhard Brenner, Robert Zweigerdt, Theresia Kraft
Human pluripotent stem cell (hPSC)-derived cardiomyocytes hold great potential for in vitro modeling of diseases like cardiomyopathies. Yet, knowledge about expression and functional impact of sarcomeric protein isoforms like the myosin heavy chain (MyHC) in hPSC-cardiomyocytes is scarce. We hypothesized that ventricular β-MyHC expression alters contraction and calcium kinetics and drives morphological and electrophysiological differentiation towards ventricular-like cardiomyocytes. To address this, we (1) generated human embryonic stem cell-derived cardiomyocytes (hESC-CMs) that switched towards exclusive β-MyHC, and (2) functionally and morphologically characterized these hESC-CMs at the single-cell level...
November 2016: Basic Research in Cardiology
https://www.readbyqxmd.com/read/27703000/palmitoylation-of-desmoglein-2-is-a-regulator-of-assembly-dynamics-and-protein-turnover
#4
Brett J Roberts, Robert A Svoboda, Andrew M Overmiller, Joshua D Lewis, Andrew P Kowalczyk, My G Mahoney, Keith R Johnson, James K Wahl
Desmosomes are prominent adhesive junctions present between many epithelial cells as well as cardiomyocytes. The mechanisms controlling desmosome assembly and remodeling in epithelial and cardiac tissue are poorly understood. We recently identified protein palmitoylation as a mechanism regulating desmosome dynamics. In this study, we have focused on the palmitoylation of the desmosomal cadherin desmoglein-2 (Dsg2) and characterized the role that palmitoylation of Dsg2 plays in its localization and stability in cultured cells...
November 25, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27670941/microgravity-induces-proteomics-changes-involved-in-endoplasmic-reticulum-stress-and-mitochondrial-protection
#5
Bryan J Feger, J Will Thompson, Laura G Dubois, Reddy P Kommaddi, Matthew W Foster, Rajashree Mishra, Sudha K Shenoy, Yoichiro Shibata, Yared H Kidane, M Arthur Moseley, Lisa S Carnell, Dawn E Bowles
On Earth, biological systems have evolved in response to environmental stressors, interactions dictated by physical forces that include gravity. The absence of gravity is an extreme stressor and the impact of its absence on biological systems is ill-defined. Astronauts who have spent extended time under conditions of minimal gravity (microgravity) experience an array of biological alterations, including perturbations in cardiovascular function. We hypothesized that physiological perturbations in cardiac function in microgravity may be a consequence of alterations in molecular and organellar dynamics within the cellular milieu of cardiomyocytes...
September 27, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27572127/endogenous-mechanisms-of-cardiac-regeneration
#6
M S W Xiang, K Kikuchi
Zebrafish possess a remarkable capacity for cardiac regeneration throughout their lifetime, providing a model for investigating endogenous cellular and molecular mechanisms regulating myocardial regeneration. By contrast, adult mammals have an extremely limited capacity for cardiac regeneration, contributing to mortality and morbidity from cardiac diseases such as myocardial infarction and heart failure. However, the viewpoint of the mammalian heart as a postmitotic organ was recently revised based on findings that the mammalian heart contains multiple undifferentiated cell types with cardiogenic potential as well as a robust regenerative capacity during a short period early in life...
2016: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/27545814/natural-myocardial-ecm-patch-drives-cardiac-progenitor-based-restoration-even-after-scarring
#7
Udi Sarig, Hadar Sarig, Elio de-Berardinis, Su-Yin Chaw, Evelyne B V Nguyen, Vaibavi S Ramanujam, Vu D Thang, Muthafar Al-Haddawi, Susan Liao, Dror Seliktar, Theodoros Kofidis, Freddy Y C Boey, Subbu S Venkatraman, Marcelle Machluf
OBJECTIVE: To evaluate the regenerative capacity of non-supplemented and bioactive patches made of decellularized porcine cardiac extracellular matrix (pcECM) and characterize the biological key factors involved in possible cardiac function (CF) restoration following acute and 8weeks chronic MI. BACKGROUND: pcECM is a key natural biomaterial that can affect cardiac regeneration following myocardial infarction (MI), through mechanisms, which are still not clearly understood...
October 15, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27484198/innate-heart-regeneration-endogenous-cellular-sources-and-exogenous-therapeutic-amplification
#8
Konstantinos Malliaras, Styliani Vakrou, Chris J Kapelios, John N Nanas
INTRODUCTION: The -once viewed as heretical- concept of the adult mammalian heart as a dynamic organ capable of endogenous regeneration has recently gained traction. However, estimated rates of myocyte turnover vary wildly and the underlying mechanisms of cardiac plasticity remain controversial. It is still unclear whether the adult mammalian heart gives birth to new myocytes through proliferation of resident myocytes, through cardiomyogenic differentiation of endogenous progenitors or through both mechanisms...
November 2016: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/27474266/temporal-partitioning-of-cardiac-metabolism-by-the-cardiomyocyte-circadian-clock
#9
Martin E Young
What is the topic of this review? This review highlights temporal partitioning of cardiac metabolism by the cardiomyocyte circadian clock. What advances does it highlight? Advances include: 1) cardiac glucose utilization peaks during the active period to meet increased energetic demands at this time; 2) synthesis of glycogen and triglyceride peak in the heart during the latter half of the active period, likely in anticipation of the upcoming sleep/fasting period; and 3) protein turnover increases in the heart at the beginning of the sleep phase, probably to promote growth and repair at this time...
August 1, 2016: Experimental Physiology
https://www.readbyqxmd.com/read/27421947/cardiac-ubiquitin-ligases-their-role-in-cardiac-metabolism-autophagy-cardioprotection-and-therapeutic-potential
#10
Traci L Parry, Monte S Willis
Both the ubiquitin-proteasome system (UPS) and the lysosomal autophagy system have emerged as complementary key players responsible for the turnover of cellular proteins. The regulation of protein turnover is critical to cardiomyocytes as post-mitotic cells with very limited regenerative capacity. In this focused review, we describe the emerging interface between the UPS and autophagy, with E3's regulating autophagy at two critical points through multiple mechanisms. Moreover, we discuss recent insights in how both the UPS and autophagy can alter metabolism at various levels, to present new ways to think about therapeutically regulating autophagy in a focused manner to optimize disease-specific cardioprotection, without harming the overall homeostasis of protein quality control...
July 13, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27412473/the-role-of-ampk-in-cardiomyocyte-health-and-survival
#11
Suresh C Bairwa, Nirmal Parajuli, Jason R B Dyck
Cellular energy homeostasis is a fundamental process that governs the overall health of the cell and is paramount to cell survival. Central to this is the control of ATP generation and utilization, which is regulated by a complex myriad of enzymatic reactions controlling cellular metabolism. In the cardiomyocyte, ATP generated from substrate catabolism is used for numerous cellular processes including maintaining ionic homeostasis, cell repair, protein synthesis and turnover, organelle turnover, and contractile function...
July 10, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27340841/scanning-electron-microscopy-of-macerated-tissue-to-visualize-the-extracellular-matrix
#12
Matthew K Stephenson, Sean Lenihan, Roman Covarrubias, Ryan M Huttinger, Richard J Gumina, Douglas B Sawyer, Cristi L Galindo
Fibrosis is a component of all forms of heart disease regardless of etiology, and while much progress has been made in the field of cardiac matrix biology, there are still major gaps related to how the matrix is formed, how physiological and pathological remodeling differ, and most importantly how matrix dynamics might be manipulated to promote healing and inhibit fibrosis. There is currently no treatment option for controlling, preventing, or reversing cardiac fibrosis. Part of the reason is likely the sheer complexity of cardiac scar formation, such as occurs after myocardial infarction to immediately replace dead or dying cardiomyocytes...
2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27285379/simultaneous-assessment-of-cardiomyocyte-dna-synthesis-and-ploidy-a-method-to-assist-quantification-of-cardiomyocyte-regeneration-and-turnover
#13
Gavin D Richardson
Although it is accepted that the heart has a limited potential to regenerate cardiomyocytes following injury and that low levels of cardiomyocyte turnover occur during normal ageing, quantification of these events remains challenging. This is in part due to the rarity of the process and the fact that multiple cellular sources contribute to myocardial maintenance. Furthermore, DNA duplication within cardiomyocytes often leads to a polyploid cardiomyocyte and only rarely leads to new cardiomyocytes by cellular division...
May 23, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27074051/endoplasmic-reticulum-stress-is-involved-in-dfmo-attenuating-isoproterenol-induced-cardiac-hypertrophy-in-rats
#14
Yan Lin, Xiaojie Zhang, Wei Xiao, Bo Li, Jun Wang, Li Jin, Jie Lian, Li Zhou, Jicheng Liu
BACKGROUND/AIMS: Studies performed in experimental animals have shown that polyamines contribute to several physiological and pathological processes, including cardiac hypertrophy. This involves an increase in ornithine decarboxylase (ODC) activity and intracellular polyamines associated with regulation of gene expression. Difluoromethylornithine (DFMO), an irreversible inhibitor of ODC, has attracted considerable interest for its antiproliferative role, which it exerts through inhibition of the polyamine pathway and cell turnover...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27021517/ablation-of-cardiac-myosin-binding-protein-c-disrupts-the-super-relaxed-state-of-myosin-in-murine-cardiomyocytes
#15
James W McNamara, Amy Li, Nicola J Smith, Sean Lal, Robert M Graham, Kristina Bezold Kooiker, Sabine J van Dijk, Cristobal G Dos Remedios, Samantha P Harris, Roger Cooke
Cardiac myosin binding protein-C (cMyBP-C) is a structural and regulatory component of cardiac thick filaments. It is observed in electron micrographs as seven to nine transverse stripes in the central portion of each half of the A band. Its C-terminus binds tightly to the myosin rod and contributes to thick filament structure, while the N-terminus can bind both myosin S2 and actin, influencing their structure and function. Mutations in the MYBPC3 gene (encoding cMyBP-C) are commonly associated with hypertrophic cardiomyopathy (HCM)...
May 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/27019087/omega-3-fatty-acids-do-not-protect-against-arrhythmias-in-acute-nonreperfused-myocardial-infarction-despite-some-antiarrhythmic-effects
#16
Michał Mączewski, Monika Duda, Mariusz Marciszek, Joanna Kołodziejczyk, Paweł Dobrzyń, Agnieszka Dobrzyń, Urszula Mackiewicz
Ventricular arrhythmias are an important cause of mortality in the acute myocardial infarction (MI). To elucidate the effect of the omega-3 polyunsaturated fatty acids (PUFAs) on ventricular arrhythmias in acute nonreperfused MI, rats were fed with normal or eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA)-enriched diet for 3 weeks. Subsequently the rats were subjected to either MI induction or sham operation. ECG was recorded for 6 h after the operation and episodes of ventricular tachycardia/fibrillation (VT/VF) were identified...
November 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/26995156/acyl-coa-synthetase-1-links-facilitated-long-chain-fatty-acid-uptake-to-intracellular-metabolic-trafficking-differently-in-hearts-of-male-versus-female-mice
#17
Joseph R Goldenberg, Xuerong Wang, E Douglas Lewandowski
RATIONALE: Acyl CoA synthetase-1 (ACSL1) is localized at intracellular membranes, notably the mitochondrial membrane. ACSL1 and female sex are suggested to indirectly facilitate lipid availability to the heart and other organs. However, such mechanisms in intact, functioning myocardium remain unexplored, and roles of ACSL1 and sex in the uptake and trafficking of fats are poorly understood. OBJECTIVE: To determine the potential for ACSL1 and sex-dependent differences in metabolic trapping and trafficking effects of long-chain fatty acids (LCFA) within cardiomyocytes of intact hearts...
May 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/26993578/triacylglycerol-turnover-in-the-failing-heart
#18
REVIEW
Andrew N Carley, E Douglas Lewandowski
No longer regarded as physiologically inert the endogenous triacylglyceride (TAG) pool within the cardiomyocyte is now recognized to play a dynamic role in metabolic regulation. Beyond static measures of content, the relative rates of interconversion among acyl intermediates are more closely linked to dynamic processes of physiological function in normal and diseased hearts, with the potential for both adaptive and maladaptive contributions. Indeed, multiple inefficiencies in cardiac metabolism have been identified in the decompensated, hypertrophied and failing heart...
October 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/26992930/central-parkin-the-evolving-role-of-parkin-in-the-heart
#19
REVIEW
Gerald W Dorn
Parkin is familiar to many because of its link to Parkinson's disease, and to others because of its well-characterized role as a central factor mediating selective mitophagy of damaged mitochondria for mitochondrial quality control. The genetic connection between Parkin and Parkinson's disease derives from clinical gene-association studies, whereas our mechanistic understanding of Parkin functioning in mitophagy is based almost entirely on work performed in cultured cells. Surprisingly, experimental evidence linking the disease and the presumed mechanism derives almost entirely from fruit flies; germline Parkin deficient mice do not develop Parkinson's disease phenotypes...
August 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/26924251/fat-in-the-heart-the-enzymatic-machinery-regulating-cardiac-triacylglycerol-metabolism
#20
REVIEW
Christoph Heier, Guenter Haemmerle
The heart predominantly utilizes fatty acids (FAs) as energy substrate. FAs that enter cardiomyocytes can be activated and directly oxidized within mitochondria (and peroxisomes) or they can be esterified and intracellularly deposited as triacylglycerol (TAG) often simply referred to as fat. An increase in cardiac TAG can be a signature of the diseased heart and may implicate a minor role of TAG synthesis and breakdown in normal cardiac energy metabolism. Often overlooked, the heart has an extremely high TAG turnover and the transient deposition of FAs within the cardiac TAG pool critically determines the availability of FAs as energy substrate and signaling molecules...
October 2016: Biochimica et Biophysica Acta
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