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cardiomyocyte and metabolism

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https://www.readbyqxmd.com/read/28095410/cardiomyocyte-regulation-of-systemic-lipid-metabolism-by-the-apolipoprotein-b-containing-lipoproteins-in-drosophila
#1
Sunji Lee, Hong Bao, Zachary Ishikawa, Weidong Wang, Hui-Ying Lim
The heart has emerged as an important organ in the regulation of systemic lipid homeostasis; however, the underlying mechanism remains poorly understood. Here, we show that Drosophila cardiomyocytes regulate systemic lipid metabolism by producing apolipoprotein B-containing lipoproteins (apoB-lipoproteins), essential lipid carriers that are so far known to be generated only in the fat body. In a Drosophila genetic screen, we discovered that when haplo-insufficient, microsomal triglyceride transfer protein (mtp), required for the biosynthesis of apoB-lipoproteins, suppressed the development of diet-induced obesity...
January 17, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28069669/refining-the-molecular-organization-of-the-cardiac-intercalated-disc
#2
REVIEW
Sarah H Vermij, Hugues Abriel, Toon A B van Veen
This review presents an extensively integrated model of the cardiac intercalated disc (ID), a highly orchestrated structure that connects adjacent cardiomyocytes. Classically, three main structures are distinguished: gap junctions (GJs) metabolically and electrically connect cytoplasm of adjacent cardiomyocytes; adherens junctions (AJs) connect the actin cytoskeleton of adjacent cells; and desmosomes function as cell anchors and connect intermediate filaments. Furthermore, ion channels reside in the ID. Mutations in ID proteins have been associated with cardiac arrhythmias such as Brugada syndrome and arrhythmogenic cardiomyopathy...
January 8, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28062567/short-term-high-fat-diet-compromises-myocardial-function-a-radial-strain-rate-imaging-study
#3
Julien Ternacle, Feng Wan, Daigo Sawaki, Mathieu Surenaud, Maria Pini, Raquel Mercedes, Laura Ernande, Etienne Audureau, Jean-Luc Dubois-Rande, Serge Adnot, Sophie Hue, Gabor Czibik, Genevieve Derumeaux
AIM: Long-term high-fat diet (HFD) induces both cardiac remodelling and myocardial dysfunction in murine models. The aim was to assess the time course and mechanisms of metabolic and cardiac modifications induced by short-term HFD in wild-type (WT) mice. METHODS AND RESULTS: Thirty-three WT mice were subjected to HFD (60% fat, n = 16) and chow diet (CD, 13% fat, n = 17). Metabolic and echocardiographic data were collected at baseline and every 5 weeks for 20 weeks...
January 6, 2017: European Heart Journal Cardiovascular Imaging
https://www.readbyqxmd.com/read/28062415/cardiomyocyte-specific-ablation-of-cd36-accelerates-the-progression-from-compensated-cardiac-hypertrophy-to-heart-failure
#4
Miranda M Sung, Nikole J Byrne, Ty T Kim, Jody Levasseur, Grant Masson, Jamie Boisvenue, Maria Febbraio, Jason R B Dyck
Previous studies have shown that loss of CD36 protects the heart from dysfunction induced by pressure overload in the presence of diet-induced insulin resistance and/or obesity. The beneficial effects of CD36 ablation in this context are mediated by preventing excessive cardiac fatty acid (FA) entry and reducing lipotoxic injury. However, whether or not the loss of CD36 can prevent pressure overload-induced cardiac dysfunction in the absence of chronic exposure to high circulating FAs is currently unknown. To address this, we utilized a tamoxifen inducible cardiomyocyte-specific CD36 knockout (icCD36KO) mouse and genetically deleted CD36 in adulthood...
January 6, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28056568/in-vitro-metabolite-formation-in-human-hepatocytes-and-cardiomyocytes-and-metabolism-and-tissue-distribution-in-monkeys-of-the-2-c-methylguanosine-prodrug-bms-986094
#5
Wenying Li, Kevin J Trouba, Li Ma, Jae Kwagh, Christopher Storck, Yongxin Zhu, Oliver Flint, William G Humphreys, Jian Wang, Ang Liu, Bonnie Wang, Michael J Graziano, Marc H Davies, Thomas P Sanderson
BMS-986094, a 2'-C-methylguanosine prodrug for the treatment of chronic hepatitis C virus infection, was withdrawn from phase 2 clinical trials because of unexpected cardiac and renal toxicities. To better understand these toxicities, the in vitro metabolism of BMS-986094 in human hepatocytes (HHs) and human cardiomyocytes (HCMs) and the measurement of BMS-986094 and selected metabolites in monkey plasma and tissues were assessed. BMS-986094 was extensively metabolized by HHs and HCMs, resulting in more efficient formation and accumulation of the active triphosphorylated metabolite, INX-09114, and less efficient efflux of metabolites in HCMs...
January 1, 2017: International Journal of Toxicology
https://www.readbyqxmd.com/read/28019665/the-impact-of-left-ventricular-stretching-in-model-cultivations-with-neonatal-cardiomyocytes-in-a-whole-heart-bioreactor
#6
Jörn Hülsmann, Hug Aubin, Alexander Wehrmann, Artur Lichtenberg, Payam Akhyari
Here, we investigate the impact of integrated three-dimensional (3D) left ventricular (LV) stretching on myocardial maturation in a whole-heart bioreactor setting. Therefore, decellularized rat hearts were selectively repopulated with rodent neonatal cardiomyocytes (5•10(6) cells per heart) and cultured over 5 d. Continuous medium perfusion was maintained through the coronary artery system in a customized whole-heart bioreactor system with or without integrated biomechanical stimulation of LV. 3D repopulation effectiveness and cellular vitality were evaluated by repetitive metabolic WST-1 assays and 3D confocal microscopy analysis through fluorescent staining, also assessing cellular organization...
December 26, 2016: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28017777/the-cardioprotective-effect-of-sildenafil-is-mediated-by-the-activation-of-malate-dehydrogenase-and-an-increase-in-the-malate-aspartate-shuttle-in-cardiomyocytes
#7
Gevi Federica, Campolo Federica, Naro Fabio, Zolla Lello
Recent evidence has shown showed the cardioprotective effect of PDE5 inhibition in myocardial ischemia/reperfusion injury, heart failure and cardiac hypertrophy. To investigate the biochemical changes that occur during PDE5 inhibition in cardiac cells, this study assessed the metabolic profile of the HL1 cell line, a murine atrial cell line with adult cardiomyocyte properties. After one hour of treatment with sildenafil, glycolysis was moderately but selectively stimulated, unlike the pentose phosphate pathway and the Krebs cycle...
December 22, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28011589/maternal-engineered-nanomaterial-exposure-disrupts-progeny-cardiac-function-and-bioenergetics
#8
Quincy A Hathaway, Cody E Nichols, Danielle L Shepherd, Phoebe A Stapleton, Sarah L Mclaughlin, Janelle C Stricker, Stephanie L Rellick, Mark V Pinti, Alaeddin B Abukabda, Caroll R McBride, Jinghai Yi, Seth M Stine, Timothy R Nurkiewicz, John M Hollander
Nanomaterial production is expanding as new industrial and consumer applications are introduced. Nevertheless, the impacts of exposure to these compounds are not fully realized. The current study was designed to determine whether gestational nano-TiO2 exposure impacts cardiac and metabolic function of developing progeny. Pregnant Sprague Dawley rats were exposed to nano-TiO2 aerosols (~10 mg/m(3), 130 - 150 nm count median aerodynamic diameter) for 7-8 non-consecutive days beginning at gestational day 5-6. Physiological and bioenergetic effects on heart function and cardiomyocytes across three time points: fetal (gestational day 20), neonatal (4-10 days), and young adult (6-12 weeks) were evaluated...
December 23, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28004807/expert-consensus-document-mitochondrial-function-as-a-therapeutic-target-in-heart-failure
#9
David A Brown, Justin B Perry, Mitchell E Allen, Hani N Sabbah, Brian L Stauffer, Saame Raza Shaikh, John G F Cleland, Wilson S Colucci, Javed Butler, Adriaan A Voors, Stefan D Anker, Bertram Pitt, Burkert Pieske, Gerasimos Filippatos, Stephen J Greene, Mihai Gheorghiade
Heart failure is a pressing worldwide public-health problem with millions of patients having worsening heart failure. Despite all the available therapies, the condition carries a very poor prognosis. Existing therapies provide symptomatic and clinical benefit, but do not fully address molecular abnormalities that occur in cardiomyocytes. This shortcoming is particularly important given that most patients with heart failure have viable dysfunctional myocardium, in which an improvement or normalization of function might be possible...
December 22, 2016: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/27995363/unacylated-ghrelin-analog-prevents-myocardial-reperfusion-injury-independently-of-permeability-transition-pore
#10
Rania Harisseh, Bruno Pillot, Abdallah Gharib, Lionel Augeul, Noelle Gallo-Bona, René Ferrera, Joseph Loufouat, Thomas Delale, Soraya Allas, Thierry Abribat, Claire Crola Da Silva, Michel Ovize
Reperfusion injury is responsible for an important part of myocardial infarct establishment due notably to triggering cardiomyocytes death at the first minutes of reperfusion. AZP-531 is an optimized analog of unacylated ghrelin currently in clinical development in several metabolic diseases. We investigated a potential cardioprotective effect of AZP-531 in ischemia/reperfusion (IR) and the molecular underlying mechanism(s) involved in this protection. In vivo postconditioning with AZP-531 in C57BL6 mouse IR model decreased infarct size...
January 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/27989687/the-role-of-protein-kinase-c-in-the-metabolic-regulation-of-the-cardiac-na-channel
#11
Man Liu, Guangbin Shi, Kai-Chien Yang, Lianzhi Gu, Anumantha G Kanthasany, Vellareddy Anantharam, Samuel C Dudley
BACKGROUND: NADH increases in cardiomyopathy, activates protein kinase C (PKC), upregulates mitochondrial reactive oxygen species (mitoROS), and downregulates the cardiac Na(+) channel (Nav1.5). OBJECTIVE: The objective was to determine how NADH signals downregulation of Nav1.5. METHODS: Isolated mouse cardiomyocytes were used for patch clamp recording and to monitor mitoROS with MitoSOX(TM) Red. HEK293 cells were used for transient transfections...
December 15, 2016: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/27984724/disease-model-of-gata4-mutation-reveals-transcription-factor-cooperativity-in-human-cardiogenesis
#12
Yen-Sin Ang, Renee N Rivas, Alexandre J S Ribeiro, Rohith Srivas, Janell Rivera, Nicole R Stone, Karishma Pratt, Tamer M A Mohamed, Ji-Dong Fu, C Ian Spencer, Nathaniel D Tippens, Molong Li, Anil Narasimha, Ethan Radzinsky, Anita J Moon-Grady, Haiyuan Yu, Beth L Pruitt, Michael P Snyder, Deepak Srivastava
Mutation of highly conserved residues in transcription factors may affect protein-protein or protein-DNA interactions, leading to gene network dysregulation and human disease. Human mutations in GATA4, a cardiogenic transcription factor, cause cardiac septal defects and cardiomyopathy. Here, iPS-derived cardiomyocytes from subjects with a heterozygous GATA4-G296S missense mutation showed impaired contractility, calcium handling, and metabolic activity. In human cardiomyocytes, GATA4 broadly co-occupied cardiac enhancers with TBX5, another transcription factor that causes septal defects when mutated...
December 15, 2016: Cell
https://www.readbyqxmd.com/read/27980224/influence-of-aging-on-the-activity-of-mice-sca-1-cd31-cardiac-stem-cells
#13
Qiong Wu, Jinxi Zhan, Shiming Pu, Liu Qin, Yun Li, Zuping Zhou
Therapeutic application of cardiac resident stem/progenitor cells (CSC/CPCs) is limited due to decline of their regenerative potential with donor age. A variety of studies have shown that the cardiac aging was the problem of the stem cells, but little is known about the impact of age on the subgroups CSC/CPCs, the relationship between subgroups CSC/CPCs ageing and age-related dysfunction. Here, we studied Sca-1+CD31- subgroups of CSCs from younger(2~3months) and older(22~24months) age mice, biological differentiation was realized using specific mediums for 14 days to induce cardiomyocyte, smooth muscle cells or endothelial cells and immunostain analysis of differentiated cell resulting were done...
December 14, 2016: Oncotarget
https://www.readbyqxmd.com/read/27979811/high-glucose-facilitated-endothelial-heparanase-transfer-to-the-cardiomyocyte-modifies-its-cell-death-signature
#14
Fulong Wang, Jocelyn Jia, Nathaniel Lal, Dahai Zhang, Amy Pei-Ling Chiu, Andrea Wan, Israel Vlodavsky, Bahira Hussein, Brian Rodrigues
AIMS: The secretion of enzymatically active heparanase (Hep(A)) has been implicated as an essential metabolic adaptation in the heart following diabetes. However, the regulation and function of the enzymatically inactive heparanase (Hep(L)) remain poorly understood. We hypothesized that in response to high glucose (HG) and secretion of Hep(L) from the endothelial cell (EC), Hep(L) uptake and function can protect the cardiomyocyte by modifying its cell death signature. METHODS AND RESULTS: HG promoted both Hep(L) and Hep(A) secretion from microvascular (rat heart micro vessel endothelial cells, RHMEC) and macrovascular (rat aortic endothelial cells, RAOEC) EC...
December 2016: Cardiovascular Research
https://www.readbyqxmd.com/read/27974512/murine-electrophysiological-models-of-cardiac-arrhythmogenesis
#15
REVIEW
Christopher L-H Huang
Cardiac arrhythmias can follow disruption of the normal cellular electrophysiological processes underlying excitable activity and their tissue propagation as coherent wavefronts from the primary sinoatrial node pacemaker, through the atria, conducting structures and ventricular myocardium. These physiological events are driven by interacting, voltage-dependent, processes of activation, inactivation, and recovery in the ion channels present in cardiomyocyte membranes. Generation and conduction of these events are further modulated by intracellular Ca(2+) homeostasis, and metabolic and structural change...
January 2017: Physiological Reviews
https://www.readbyqxmd.com/read/27966485/metabolic-alterations-derived-from-absence-of-two-pore-channel-1-at-cardiac-level
#16
Vanessa Garcia-Rua, Sandra Feijoo-Bandin, Maria Garcia-Vence, Alana Aragon-Herrera, Susana B Bravo, Diego Rodriguez-Penas, Ana Mosquera-Leal, Pamela V Lear, John Parrington, Jana Alonso, Esther Rosello-Lleti, Manuel Portoles, Miguel Rivera, Jose Ramon Gonzalez-Juanatey, Francisca Lago
Two-pore channels (TPCs or TPCNs) are novel voltage-gated ion channels that have been postulated to act as Ca2+ and/or Na+ channels expressed exclusively in acidic organelles such as endosomes and lysosomes. TPCNs participate in the regulation of diverse biological processes and recently have been proposed to be involved in the pathophysiology of metabolic disorders such as obesity, fatty liver disease and type 2 diabetes mellitus. Due to the importance of these pathologies in the development of cardiovascular diseases, we aimed to study the possible role of two-pore channel 1 (TPCN1) in the regulation of cardiac metabolism...
December 2016: Journal of Biosciences
https://www.readbyqxmd.com/read/27941349/lipotoxic-palmitate-impairs-the-rate-of-%C3%AE-oxidation-and-citric-acid-cycle-flux-in-rat-neonatal-cardiomyocytes
#17
Taha Haffar, Ali Akoumi, Nicolas Bousette
BACKGROUND/AIMS: Diabetic hearts exhibit intracellular lipid accumulation. This suggests that the degree of fatty acid oxidation (FAO) in these hearts is insufficient to handle the elevated lipid uptake. We previously showed that palmitate impaired the rate of FAO in primary rat neonatal cardiomyocytes. Here we were interested in characterizing the site of FAO impairment induced by palmitate since it may shed light on the metabolic dysfunction that leads to lipid accumulation in diabetic hearts...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27933370/doxorubicin-induced-chronic-dilated-cardiomyopathy-the-apoptosis-hypothesis-revisited
#18
REVIEW
Cynthia Kankeu, Kylie Clarke, Egle Passante, Heinrich J Huber
The chemotherapeutic agent doxorubicin (DOX) has significantly increased survival rates of pediatric and adult cancer patients. However, 10% of pediatric cancer survivors will 10-20 years later develop severe dilated cardiomyopathy (DCM), whereby the exact molecular mechanisms of disease progression after this long latency time remain puzzling. We here revisit the hypothesis that elevated apoptosis signaling or its increased likelihood after DOX exposure can lead to an impairment of cardiac function and cause a cardiac dilation...
December 8, 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/27931032/fatty-acid-oxidation-and-its-relation-with-insulin-resistance-and-associated-disorders
#19
Gary D Lopaschuk
Alterations in muscle fatty acid metabolism have been implicated in mediating the severity of insulin resistance. In the insulin resistant heart fatty acids are favored as an energy source over glucose, which is thus associated with increased fatty acid oxidation, and an overall decrease in glycolysis and glucose oxidation. In addition, excessive uptake and beta-oxidation of fatty acids in obesity and diabetes can compromise cardiac function. In animal studies, mice fed a high fat diet (HFD) show cardiac insulin resistance in which the accumulation of intra-myocardial diacylglycerol has been implicated, likely involving parallel signaling pathways...
2016: Annals of Nutrition & Metabolism
https://www.readbyqxmd.com/read/27907040/the-role-of-reactive-oxygen-species-in-%C3%AE-adrenergic-signaling-in-cardiomyocytes-from-mice-with-the-metabolic-syndrome
#20
Monica Llano-Diez, Jon Sinclair, Takashi Yamada, Mei Zong, Jeremy Fauconnier, Shi-Jin Zhang, Abram Katz, Kent Jardemark, Håkan Westerblad, Daniel C Andersson, Johanna T Lanner
The metabolic syndrome is associated with prolonged stress and hyperactivity of the sympathetic nervous system and afflicted subjects are prone to develop cardiovascular disease. Under normal conditions, the cardiomyocyte response to acute β-adrenergic stimulation partly depends on increased production of reactive oxygen species (ROS). Here we investigated the interplay between beta-adrenergic signaling, ROS and cardiac contractility using freshly isolated cardiomyocytes and whole hearts from two mouse models with the metabolic syndrome (high-fat diet and ob/ob mice)...
2016: PloS One
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