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cardiomyocyte and metabolism

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https://www.readbyqxmd.com/read/29792884/pharmacological-inhibition-of-dna-methylation-attenuates-pressure-overload-induced-cardiac-hypertrophy-in-rats
#1
Justus Stenzig, Yvonne Schneeberger, Alexandra Löser, Barbara S Peters, Andreas Schaefer, Rong-Rong Zhao, Shi Ling Ng, Grit Höppner, Birgit Geertz, Marc N Hirt, Wilson Tan, Eleanor Wong, Hermann Reichenspurner, Roger S-Y Foo, Thomas Eschenhagen
BACKGROUND: Heart failure is associated with altered gene expression and DNA methylation. De novo DNA methylation is associated with gene silencing, but its role in cardiac pathology remains incompletely understood. We hypothesized that inhibition of DNA methyltransferases (DNMT) might prevent the deregulation of gene expression and the deterioration of cardiac function under pressure overload (PO). To test this hypothesis, we evaluated a DNMT inhibitor in PO in rats and analysed DNA methylation in cardiomyocytes...
May 21, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29791204/role-of-adenosine-signaling-in-coordinating-cardiomyocyte-function-and-coronary-vascular-growth-in-chronic-fetal-anemia
#2
Lowell Davis, James Musso, Divya Soman, Samantha Louey, Jonathan William Nelson, Sonnet S Jonker
Fetal anemia causes rapid and profound changes in cardiac structure and function, stimulating proliferation of the cardiac myocytes, expansion of the coronary vascular tree, and impairing early contraction and relaxation. While HIF-1α is sure to play a role, adenosine, a metabolic byproduct that increases coronary flow and growth, is implicated as a major stimulus for these adaptations. We hypothesized that genes involved in myocardial adenosine signaling would be up-regulated in chronically anemic fetuses, and that calcium handling genes would be down-regulated...
May 23, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29789564/establishing-quasi-steady-state-operations-of-microphysiological-systems-mps-using-tissue-specific-metabolic-dependencies
#3
Christian Maass, Matthew Dallas, Matthew E LaBarge, Michael Shockley, Jorge Valdez, Emily Geishecker, Cynthia L Stokes, Linda G Griffith, Murat Cirit
Microphysiological systems (MPS), consisting of tissue constructs, biomaterials, and culture media, aim to recapitulate relevant organ functions in vitro. MPS components are housed in fluidic hardware with operational protocols, such as periodic complete media replacement. Such batch-like operations provide relevant nutrients and remove waste products but also reset cell-secreted mediators (e.g. cytokines, hormones) and potentially limit exposure to drugs (and metabolites). While each component plays an essential role for tissue functionality, MPS-specific nutrient needs are not yet well-characterized nor utilized to operate MPSs at more physiologically-relevant conditions...
May 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29777709/amelioration-of-myocardial-ischemia-reperfusion-injury-by-sirt4-involves-mitochondrial-protection-and-reduced-apoptosis
#4
Guangwei Zeng, Hui Liu, Haiyan Wang
Apoptosis and mitochondria dysfunction are key contributors to myocardial ischemia-reperfusion (MI-R) injury. SIRT4, a mitochondrial-localized sirtuin, controls cellular energy metabolism and stress response, and is abundantly present in the heart, however, its role in MI-R injury is not clear. In the current study, we demonstrate that SIRT4 is downregulated in cardiomyocytes both in vitro and in vivo models after MI-R. Functionally, SIRT4 overexpression decreases myocardial infarct size and serum creatine phosphokinase (CPK) level, and vice versa, SIRT4 depletion by siRNA increases myocardial infarct size and serum CPK level...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29772531/effects-of-oxidized-lipids-and-lipoproteins-on-cardiac-function
#5
Tahar Hajri
Oxidative modifications of lipids and lipoproteins have long been linked to the pathogenesis of cardiovascular diseases including atherosclerosis and coronary disease. Furthermore, overwhelming evidence indicate that oxidized lipids are also associated with myocardial dysfunction and cardiomyopathy. Oxidized lipid derivatives are generated by enzymatic and non-enzymatic reactions with unsaturated lipids in the cell and foods. In addition, blood LDL particles are prone to oxidation leading to the formation of oxidized LDL (oxLDL), which is often associated with obesity, diabetes and metabolic disease...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29770421/quantitative-proteomics-and-systems-analysis-of-cultured-h9c2-cardiomyoblasts-during-differentiation-over-time-supports-a-function-follows-form-model-of-differentiation
#6
Cynthia Kankeu, Kylie Clarke, Delphi Van Haver, Kris Gevaert, Francis Impens, Anna Dittrich, H Llewelyn Roderick, Egle Passante, Heinrich J Huber
The rat cardiomyoblast cell line H9C2 has emerged as a valuable tool for studying cardiac development, mechanisms of disease and toxicology. We present here a rigorous proteomic analysis that monitored the changes in protein expression during differentiation of H9C2 cells into cardiomyocyte-like cells over time. Quantitative mass spectrometry followed by gene ontology (GO) enrichment analysis revealed that early changes in H9C2 differentiation are related to protein pathways of cardiac muscle morphogenesis and sphingolipid synthesis...
May 17, 2018: Molecular omics
https://www.readbyqxmd.com/read/29769443/acetylation-contributes-to-hypertrophy-caused-maturational-delay-of-cardiac-energy-metabolism
#7
Arata Fukushima, Liyan Zhang, Alda Huqi, Victoria H Lam, Sonia Rawat, Tariq Altamimi, Cory S Wagg, Khushmol K Dhaliwal, Lisa K Hornberger, Paul F Kantor, Ivan M Rebeyka, Gary D Lopaschuk
A dramatic increase in cardiac fatty acid oxidation occurs following birth. However, cardiac hypertrophy secondary to congenital heart diseases (CHDs) delays this process, thereby decreasing cardiac energetic capacity and function. Cardiac lysine acetylation is involved in modulating fatty acid oxidation. We thus investigated what effect cardiac hypertrophy has on protein acetylation during maturation. Eighty-four right ventricular biopsies were collected from CHD patients and stratified according to age and the absence (n = 44) or presence of hypertrophy (n = 40)...
May 17, 2018: JCI Insight
https://www.readbyqxmd.com/read/29752948/functional-and-transcriptomic-insights-into-pathogenesis-of-r9c-phospholamban-mutation-using-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#8
Delaine K Ceholski, Irene C Turnbull, Chi-Wing Kong, Simon Koplev, Joshua Mayourian, Przemek A Gorski, Francesca Stillitano, Angelos A Skodras, Mathieu Nonnenmacher, Ninette Cohen, Johan L M Björkegren, Daniel R Stroik, Razvan L Cornea, David D Thomas, Ronald A Li, Kevin D Costa, Roger J Hajjar
Dilated cardiomyopathy (DCM) can be caused by mutations in the cardiac protein phospholamban (PLN). We used CRISPR/Cas9 to insert the R9C PLN mutation at its endogenous locus into a human induced pluripotent stem cell (hiPSC) line from an individual with no cardiovascular disease. R9C PLN hiPSC-CMs display a blunted β-agonist response and defective calcium handling. In 3D human engineered cardiac tissues (hECTs), a blunted lusitropic response to β-adrenergic stimulation was observed with R9C PLN. hiPSC-CMs harboring the R9C PLN mutation showed activation of a hypertrophic phenotype, as evidenced by expression of hypertrophic markers and increased cell size and capacitance of cardiomyocytes...
May 9, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29752038/transient-postnatal-over-nutrition-induces-long-term-alterations-in-cardiac-nlrp3-inflammasome-pathway
#9
B Siddeek, N Li, C Mauduit, H Chehade, E Rigal, J-F Tolsa, J-B Armengaud, C Yzydorczyk, M Benahmed, C Vergely, U Simeoni
BACKGROUND AND AIMS: The prevalence of obesity is increasing worldwide at an alarming rate. Altered early nutrition, in particular postnatal overfeeding (PNOF), is a risk factor for impaired cardiac function in adulthood. In the understanding of the initiation or progression of heart diseases, NLRP3 inflammasome and non-coding RNAs have been proposed as key players. In this context, the aim of this study was to decipher the role of NLRP3 inflammasome and its post transcriptional control by micro-RNAs in the regulation of cardiac metabolic function induced by PNOF in mice...
April 14, 2018: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/29741611/crispr-cas9-editing-in-human-pluripotent-stem-cell-cardiomyocytes-highlights-arrhythmias-hypocontractility-and-energy-depletion-as-potential-therapeutic-targets-for-hypertrophic-cardiomyopathy
#10
Diogo Mosqueira, Ingra Mannhardt, Jamie R Bhagwan, Katarzyna Lis-Slimak, Puspita Katili, Elizabeth Scott, Mustafa Hassan, Maksymilian Prondzynski, Stephen C Harmer, Andrew Tinker, James G W Smith, Lucie Carrier, Philip M Williams, Daniel Gaffney, Thomas Eschenhagen, Arne Hansen, Chris Denning
Aims: Sarcomeric gene mutations frequently underlie hypertrophic cardiomyopathy (HCM), a prevalent and complex condition leading to left ventricle thickening and heart dysfunction. We evaluated isogenic genome-edited human pluripotent stem cell-cardiomyocytes (hPSC-CM) for their validity to model, and add clarity to, HCM. Methods and results: CRISPR/Cas9 editing produced 11 variants of the HCM-causing mutation c.C9123T-MYH7 [(p.R453C-β-myosin heavy chain (MHC)] in 3 independent hPSC lines...
May 8, 2018: European Heart Journal
https://www.readbyqxmd.com/read/29733818/translational-regulation-by-mir-301b-upregulates-amp-deaminase-in-diabetic-hearts
#11
Yuki Tatekoshi, Masaya Tanno, Hidemichi Kouzu, Koki Abe, Takayuki Miki, Atsushi Kuno, Toshiyuki Yano, Satoko Ishikawa, Wataru Ohwada, Tatsuya Sato, Takeshi Niinuma, Hiromu Suzuki, Tetsuji Miura
AMP deaminase (AMPD) plays a crucial role in adenine nucleotide metabolism. Recently we found that upregulated AMPD activity is associated with ATP depletion and contractile dysfunction under the condition of pressure overloading in the heart of a rat model of type 2 diabetes mellitus (T2DM), OLETF. Here we examined the mechanism of AMPD upregulation by T2DM. The protein level of 90-kDa full-length AMPD3 was increased in whole myocardial lysates by 55% in OLETF compared to those in LETO, a non-diabetic control...
May 4, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29732743/regulation-of-autophagy-by-tea-polyphenols-in-diabetic-cardiomyopathy
#12
Hui Zhou, Yan Chen, Shu-Wei Huang, Peng-Fei Hu, Li-Jiang Tang
OBJECTIVE: To investigate the effect of tea polyphenols on cardiac function in rats with diabetic cardiomyopathy, and the mechanism by which tea polyphenols regulate autophagy in diabetic cardiomyopathy. METHODS: Sixty Sprague-Dawley (SD) rats were randomly divided into six groups: a normal control group (NC), an obesity group (OB), a diabetic cardiomyopathy group (DCM), a tea polyphenol group (TP), an obesity tea polyphenol treatment group (OB-TP), and a diabetic cardiomyopathy tea polyphenol treatment group (DCM-TP)...
May 2018: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/29731023/heart-failure-with-preserved-ejection-fraction-in-diabetes-mechanisms-and-management
#13
REVIEW
Patrick Meagher, Mohamed Adam, Robert Civitarese, Antoinette Bugyei-Twum, Kim A Connelly
Diabetes mellitus (DM) is a major cause of heart failure in the Western world, either secondary to coronary artery disease or from a distinct entity known as "diabetic cardiomyopathy." Furthermore, heart failure with preserved ejection fraction (HFpEF) is emerging as a significant clinical problem for patients with DM. Current clinical data suggest that between 30% and 40% of patients with HFpEF suffer from DM. The typical structural phenotype of the HFpEF heart consists of endothelial dysfunction, increased interstitial and perivascular fibrosis, cardiomyocyte stiffness, and hypertrophy along with advanced glycation end products deposition...
May 2018: Canadian Journal of Cardiology
https://www.readbyqxmd.com/read/29730342/nf-%C3%AE%C2%BAb-mediated-metabolic-remodelling-in-the-inflamed-heart-in-acute-viral-myocarditis
#14
Alexander H V Remels, Wouter J A Derks, Berta Cillero-Pastor, Koen J P Verhees, Marco C Kelders, Ward Heggermont, Paolo Carai, Georg Summer, Shane R Ellis, Chiel C de Theije, Ron M A Heeren, Stephane Heymans, Ana P Papageorgiou, Marc van Bilsen
Acute viral myocarditis (VM), characterised by leukocytes infiltration and dysfunction of the heart, is an important cause of sudden cardiac death in young adults. Unfortunately, to date, the pathological mechanisms underlying cardiac failure in VM remain incompletely understood. In the current study, we investigated if acute VM leads to cardiac metabolic rewiring and if this process is driven by local inflammation. Transcriptomic analysis of cardiac biopsies from myocarditis patients and a mouse model of VM revealed prominent reductions in the expression of a multitude of genes involved in mitochondrial oxidative energy metabolism...
May 3, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29728018/-analysis-on-component-target-pathway-of-paeonia-lactiflora-in-treating-cardiac-diseases-based-on-data-mining
#15
Yang Liu, Fang-Bo Zhang, Shi-Huan Tang, Ping Wang, Sen Li, Jin Su, Rong-Rong Zhou, Jia-Qi Zhang, Hui-Feng Sun
Based on the literature review and modern application of Paeonia lactiflora in heart diseases, this article would predict the target of drug and disease by intergrative pharmacology platform of traditional Chinese medicine (TCMIP, http://www.tcmip.cn), and then explore the molecular mechanism of P. lactiflora in treatment of heart disease, providing theoretical basis and method for further studies on P. lactiflora. According to the ancient books, P. lactiflora with functions of "removing the vascular obstruction, removing the lumps, relieving pain, diuretic, nutrient qi" and other effects, have been used for many times to treat heart disease...
April 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29719224/nanosims-analysis-of-intravascular-lipolysis-and-lipid-movement-across-capillaries-and-into-cardiomyocytes
#16
Cuiwen He, Thomas A Weston, Rachel S Jung, Patrick Heizer, Mikael Larsson, Xuchen Hu, Christopher M Allan, Peter Tontonoz, Karen Reue, Anne P Beigneux, Michael Ploug, Andrea Holme, Matthew Kilburn, Paul Guagliardo, David A Ford, Loren G Fong, Stephen G Young, Haibo Jiang
The processing of triglyceride-rich lipoproteins (TRLs) in capillaries provides lipids for vital tissues, but our understanding of TRL metabolism is limited, in part because TRL processing and lipid movement have never been visualized. To investigate the movement of TRL-derived lipids in the heart, mice were given an injection of [2 H]triglyceride-enriched TRLs, and the movement of 2 H-labeled lipids across capillaries and into cardiomyocytes was examined by NanoSIMS. TRL processing and lipid movement in tissues were extremely rapid...
May 1, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29703741/hyperpolarised-magnetic-resonance-for-in-vivo-real-time-metabolic-imaging
#17
REVIEW
Andrew Apps, Justin Lau, Mark Peterzan, Stefan Neubauer, Damian Tyler, Oliver Rider
Although non-invasive perfusion and viability imaging often provide the gateway to coronary revascularisation, current non-invasive imaging methods only report the surrogate markers of inducible hypoperfusion and presence or absence of myocardial scar, rather than actually visualising areas of ischaemia and/or viable myocardium. This may lead to suboptimal revascularisation decisions. Normally respiring (viable) cardiomyocytes convert pyruvate to acetyl-CoA and CO2 /bicarbonate (via pyruvate dehydrogenase), but under ischaemic conditions characteristically shift this conversion to lactate (by lactate dehydrogenase)...
April 27, 2018: Heart: Official Journal of the British Cardiac Society
https://www.readbyqxmd.com/read/29703330/screening-and-analysis-of-key-active-constituents-in-guanxinshutong-capsule-using-mass-spectrum-and-integrative-network-pharmacology
#18
Feng Liu, Xia DU, Pei-Rong Liu, Yu-Hong Sun, Yan-Min Zhang
Guanxinshutong capsule (GXSTC) is an effective and safe traditional Chinese medicine used in the treatment of cardiovascular diseases (CVDs) for many years. However, the targets of this herbal formula and the underlying molecular mechanisms of action involved in the treatment of CVDs are still unclear. In the present study, we used a systems pharmacology approach to identify the active ingredients of GXSTC and their corresponding targets in the calcium signaling pathway with respect to the treatment of CVDs...
April 2018: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/29702047/pharmaceutical-characterization-of-myonovin-a-novel-skeletal-muscle-regenerator-in-silico-in-vitro-and-in-vivo-studies
#19
Samaa Alrushaid, Neal M Davies, Judy E Anderson, Tyson Le, Jaime A Yáñez, Zaid H Maayah, Ayman O S El-Kadi, Ousama Rachid, Casey L Sayre, Raimar Löbenberg, Frank J Burczynski
PURPOSE: MyoNovin is a novel skeletal muscle-regenerating compound developed through synthesis of two nitro groups onto a guaifenesin backbone to deliver nitric oxide to skeletal muscle with a potential to treat muscle atrophy. The purpose of this study was to utilize in silico, in vitro, and in vivo approaches to characterize MyoNovin and examine its safety, biodistribution, and feasibility for drug delivery. METHODS: In silico software packages were used to predict the physicochemical and biopharmaceutical properties of MyoNovin...
2018: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29695975/characterizing-the-key-metabolic-pathways-of-the-neonatal-mouse-heart-using-a-quantitative-combinatorial-omics-approach
#20
Maciej M Lalowski, Susann Björk, Piet Finckenberg, Rabah Soliymani, Miikka Tarkia, Giulio Calza, Daria Blokhina, Sari Tulokas, Matti Kankainen, Päivi Lakkisto, Marc Baumann, Esko Kankuri, Eero Mervaala
The heart of a newborn mouse has an exceptional capacity to regenerate from myocardial injury that is lost within the first week of its life. In order to elucidate the molecular mechanisms taking place in the mouse heart during this critical period we applied an untargeted combinatory multiomics approach using large-scale mass spectrometry-based quantitative proteomics, metabolomics and mRNA sequencing on hearts from 1-day-old and 7-day-old mice. As a result, we quantified 1.937 proteins (366 differentially expressed), 612 metabolites (263 differentially regulated) and revealed 2...
2018: Frontiers in Physiology
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