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cardiomyocyte and metabolism

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https://www.readbyqxmd.com/read/28333933/geometry-dependent-functional-changes-in-ipsc-derived-cardiomyocytes-probed-by-functional-imaging-and-rna-sequencing
#1
Christopher A Werley, Miao-Ping Chien, Jellert Gaublomme, Karthik Shekhar, Vincent Butty, B Alexander Yi, Joel M Kralj, William Bloxham, Laurie A Boyer, Aviv Regev, Adam E Cohen
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are a promising platform for cardiac studies in vitro, and possibly for tissue repair in humans. However, hiPSC-CM cells tend to retain morphology, metabolism, patterns of gene expression, and electrophysiology similar to that of embryonic cardiomyocytes. We grew hiPSC-CM in patterned islands of different sizes and shapes, and measured the effect of island geometry on action potential waveform and calcium dynamics using optical recordings of voltage and calcium from 970 islands of different sizes...
2017: PloS One
https://www.readbyqxmd.com/read/28327633/cardiac-drug-drug-interaction-between-hcv-ns5b-pronucleotide-inhibitors-and-amiodarone-is-determined-by-their-specific-diastereochemistry
#2
Armando Lagrutta, Christopher P Regan, Haoyu Zeng, John P Imredy, Kenneth Koeplinger, Pierre Morissette, Liping Liu, Gordon Wollenberg, Christopher Brynczka, José Lebrón, Joseph DeGeorge, Frederick Sannajust
Severe bradycardia/bradyarrhythmia following coadministration of the HCV-NS5B prodrug sofosbuvir with amiodarone was recently reported. Our previous preclinical in vivo experiments demonstrated that only certain HCV-NS5B prodrugs elicit bradycardia when combined with amiodarone. In this study, we evaluate the impact of HCV-NS5B prodrug phosphoramidate diastereochemistry (D-/L-alanine, R-/S-phosphoryl) in vitro and in vivo. Co-applied with amiodarone, L-ala,SP prodrugs increased beating rate and decreased beat amplitude in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), but D-ala,RP produgs, including MK-3682, did not...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28327605/ginsenoside-rb1-protects-against-ischemia-reperfusion-induced-myocardial-injury-via-energy-metabolism-regulation-mediated-by-rhoa-signaling-pathway
#3
Yuan-Chen Cui, Chun-Shui Pan, Li Yan, Lin Li, Bai-He Hu, Xin Chang, Yu-Ying Liu, Jing-Yu Fan, Kai Sun, Quan -Li, Jing-Yan Han
Cardiac ischemia and reperfusion (I/R) injury remains a challenge for clinicians. Ginsenoside Rb1 (Rb1) has been reported to have the ability to attenuate I/R injury, but its effect on energy metabolism during cardiac I/R and the underlying mechanism remain unknown. In this study, we detected the effect of Rb1 on rat myocardial blood flow, myocardial infarct size, cardiac function, velocity of venule red blood cell, myocardial structure and apoptosis, energy metabolism and change in RhoA signaling pathway during cardiac I/R injury...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28315332/nuclear-ampk-regulated-carm1-stabilization-impacts-autophagy-in-aged-heart
#4
Chen Li, Lu Yu, Han Xue, Zheng Yang, Yue Yin, Bo Zhang, Mai Chen, Heng Ma
Senescence-associated autophagy downregulation leads to cardiomyocyte dysfunction. Coactivator-associated arginine methyltransferase 1 (CARM1) participates in many cellular processes, including autophagy in mammals. However, the effect of CARM1 in aging-related cardiac autophagy decline remains undefined. Moreover, AMP-activated protein kinase (AMPK) is a key regulator in metabolism and autophagy, however, the role of nuclear AMPK in autophagy outcome in aged hearts still unclear. Hers we identify the correlation between nuclear AMPK and CARM1 in aging heart...
March 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28314760/loss-of-vegfb-and-its-signaling-in-the-diabetic-heart-is-associated-with-increased-cell-death-signaling
#5
Nathaniel Lal, Amy Pei-Ling Chiu, Fulong Wang, Dahai Zhang, Jocelyn Jia, Andrea Wan, Israel Vlodavsky, Bahira Hussein, Brian Rodrigues
VEGFB is highly expressed in metabolically active tissues, such as the heart and skeletal muscle, suggesting a function in maintaining oxidative metabolic and contractile function in these tissues. Multiple models of heart failure have indicated a significant drop in VEGFB. However, whether there is a role for decreased VEGFB in diabetic cardiomyopathy is currently unknown. Of the VEGFB located in cardiomyocytes, there is a substantial and readily releasable pool localized on the cell surface. The immediate response to high glucose and the secretion of endothelial heparanase is the release of this surface bound VEGFB, which triggers signaling pathways and gene expression to influence endothelial cell (autocrine action) and cardiomyocyte (paracrine effects) survival...
March 17, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28299467/cardiomyocyte-ogt-limits-ventricular-dysfunction-in-mice-following-pressure-overload-without-affecting-hypertrophy
#6
Sujith Dassanayaka, Robert E Brainard, Lewis J Watson, Bethany W Long, Kenneth R Brittian, Angelica M DeMartino, Allison L Aird, Anna M Gumpert, Timothy N Audam, Peter J Kilfoil, Senthilkumar Muthusamy, Tariq Hamid, Sumanth D Prabhu, Steven P Jones
The myocardial response to pressure overload involves coordination of multiple transcriptional, posttranscriptional, and metabolic cues. The previous studies show that one such metabolic cue, O-GlcNAc, is elevated in the pressure-overloaded heart, and the increase in O-GlcNAcylation is required for cardiomyocyte hypertrophy in vitro. Yet, it is not clear whether and how O-GlcNAcylation participates in the hypertrophic response in vivo. Here, we addressed this question using patient samples and a preclinical model of heart failure...
May 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28299324/micrornas-and-cardiovascular-disease-in-diabetes-mellitus
#7
REVIEW
Yue Ding, Xue Sun, Peng-Fei Shan
Cardiovascular disease (CVD) is the major macrovascular complication of diabetes mellitus. Recently, although CVD morbidity and mortality have decreased as a result of comprehensive control of CVD risk factors, CVD remains the leading cause of death of patients with diabetes in many countries, indicating the potential underlying pathophysiological mechanisms. MicroRNAs are a class of noncoding, single-stranded RNA molecules that are involved in β-cell function, insulin secretion, insulin resistance, skeletal muscle, and adipose tissue and which play an important role in glucose homeostasis and the pathogenesis of diabetic complications...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28290868/-is-it-possible-to-improve-results-in-the-conservative-treatment-strategy-in-patients-with-acute-coronary-syndrome
#8
M G Gleser, E I Astashkin, A E Kiseleva
Almost 60% of patients with acute coronary syndrome (ACS) without ST segment elevation are not subjected to revascularization procedures. This review analyzes the reasons for the choice of the conservative tactics of patients with ACS. The possibilities of improving outcomes by using modern medicines. Particular attention is given to drugs that affect energy metabolism in cardiomyocytes ischemia and reperfusion, provides data on the effect of L-carnitine on the high-risk markers, and decrease the incidence of adverse outcomes in patients with ACS...
September 2016: Kardiologiia
https://www.readbyqxmd.com/read/28288147/gestational-hyperglycemia-reprograms-cardiac-gene-expression-in-rat-offspring
#9
Lara Lehtoranta, Anna Koskinen, Olli Vuolteenaho, Jukka Laine, Ville Kytö, Hanna Soukka, Eeva Ekholm, Juha Räsänen
BACKGROUND: Rat fetuses with maternal pregestational hyperglycemia develop cardiac dysfunction and their cardiac gene expression differs from healthy control fetuses near term. HYPOTHESIS: Cardiac gene expression and morphologic abnormalities of rat fetuses with maternal pregestational hyperglycemia become normal after birth. METHODS: Nine rats were preconceptually injected with streptozotocin to induce maternal hyperglycemia and 9 rats served as controls...
March 13, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28285861/cardioprotective-effect-of-nicorandil-against-myocardial-injury-following-cardiac-arrest-in-swine
#10
Li-Ning Liang, Xia Zhong, Yi Zhou, Zhi-Qiang Hou, Hao-Ran Hu, Fang-Fang Zhu, Ji-Bin Chen, Xian-Fei Ji, De-Ya Shang
INTRODUCTION: Nicorandil, a vasodilatory drug used to treat angina, was reported to protect against myocardial ischemia-reperfusion injury in various animal models. However, its cardioprotective action following cardiac arrest is unknown. We examined the cardioprotective effects of nicorandil in a porcine model of cardiac arrest and resuscitation. METHODS: Ventricular fibrillation was induced electrically for 4min in anesthetized domestic swine, followed by cardiopulmonary resuscitation...
March 6, 2017: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28279226/the-ppar-pan-agonist-bezafibrate-ameliorates-cardiomyopathy-in-a-mouse-model-of-barth-syndrome
#11
Yan Huang, Corey Powers, Victoria Moore, Caitlin Schafer, Mindong Ren, Colin K L Phoon, Jeanne F James, Alexander V Glukhov, Sabzali Javadov, Frédéric M Vaz, John L Jefferies, Arnold W Strauss, Zaza Khuchua
BACKGROUND: The PGC-1α/PPAR axis has been proposed as a potential therapeutic target for several metabolic disorders. The aim was to evaluate the efficacy of the pan-PPAR agonist, bezafibrate, in tafazzin knockdown mice (TazKD), a mouse model of Barth syndrome that exhibits age-dependent dilated cardiomyopathy with left ventricular (LV) dysfunction. RESULTS: The effect of bezafibrate on cardiac function was evaluated by echocardiography in TazKD mice with or without beta-adrenergic stress...
March 9, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28275246/sarcoplasmic-reticulum-mitochondria-communication-in-cardiovascular-pathophysiology
#12
REVIEW
Camila Lopez-Crisosto, Christian Pennanen, Cesar Vasquez-Trincado, Pablo E Morales, Roberto Bravo-Sagua, Andrew F G Quest, Mario Chiong, Sergio Lavandero
Repetitive, calcium-mediated contractile activity renders cardiomyocytes critically dependent on a sustained energy supply and adequate calcium buffering, both of which are provided by mitochondria. Moreover, in vascular smooth muscle cells, mitochondrial metabolism modulates cell growth and proliferation, whereas cytosolic calcium levels regulate the arterial vascular tone. Physical and functional communication between mitochondria and sarco/endoplasmic reticulum and balanced mitochondrial dynamics seem to have a critical role for optimal calcium transfer to mitochondria, which is crucial in calcium homeostasis and mitochondrial metabolism in both types of muscle cells...
March 9, 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/28274939/long-term-hif-1%C3%AE-transcriptional-activation-is-essential-for-heat-acclimation-mediated-cross-tolerance-mitochondrial-target-genes
#13
Rivka Alexander-Shani, Ahmad Mreisat, Elia Smeir, Gary Gerstenblith, Michael D Stern, Michal Horowitz
An important adaptive feature of heat acclimation (AC) is the induction of cross-tolerance against novel stressors (HACT). Reprogramming of gene expression leading to enhanced innate cytoprotective features by attenuating damage and/or enhancing the response of "help" signals, plays a pivotal role. HIF-1α, constitutively upregulated by AC (1mo, 34°C), is a crucial transcription factor in this program, although its specific role is as yet unknown. By using a rat AC model we studied the impact of disrupting HIF-1α transcriptional activation [(HIF-1α:HIF-1β dimerization blockade by Acriflavine (4mg/kg b...
March 8, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28256566/aberrant-epicardial-adipose-tissue-extracellular-matrix-remodeling-in-patients-with-severe-ischemic-cardiomyopathy-insight-from-comparative-quantitative-proteomics
#14
Ding-Sheng Jiang, Hao-Long Zeng, Rui Li, Bo Huo, Yun-Shu Su, Jing Fang, Qing Yang, Li-Gang Liu, Min Hu, Cai Cheng, Xue-Hai Zhu, Xin Yi, Xiang Wei
There is ample evidence indicating that epicardial adipose tissue (EAT) volume and thickness is positively associated with coronary artery disease (CAD). However, the exact pathological changes in the human EAT after myocardial ischemia remains largely unclear. In the current study, we applied a comparative quantitative proteomics to elucidate the altered biological processes in the EAT of ischemic cardiomyopathy (ICM) patients. A total of 1649 proteins were successfully quantified in our study, among which 165 proteins were significantly changed (ratio <0...
March 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28254494/sodium-restriction-modulates-innate-immunity-and-prevents-cardiac-remodeling-in-a-rat-model-of-metabolic-syndrome
#15
Bernard Jover, Christelle Reynes, Caroline Rugale, Cyril Reboul, Laura Jeanson, Michel Tournier, Anne Dominique Lajoix, Caroline Desmetz
In the view of the relationships between excessive sodium intake, immunity and target organ damage, we hypothesized that reduction in dietary sodium would be beneficial in the prevention of cardiac alterations through a restrained local immunity response in a rat model of metabolic syndrome. Sprague-Dawley rats were fed a 60% fructose diet with either a normal sodium (0.64% NaCl) or a low sodium content (<0.01% NaCl) for 8weeks. After 4weeks, rats were infused or not with angiotensin II (200ng.kg(-1).min(-1), sc) for 4weeks...
February 27, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28253192/the-role-of-sirtuins-in-mitochondrial-function-and-doxorubicin-induced-cardiac-dysfunction
#16
Vernon W Dolinsky
Anthracycline chemotherapeutics such as doxorubicin continue to be important treatments for many cancers. Through improved screening and therapy more patients are surviving and living longer after the diagnosis of their cancer. However, anthracyclines are associated with both short- and long-term cardiotoxic effects. Doxorubicin-induced mitochondrial dysfunction is a central mechanism in the cardiotoxic effects of doxorubicin that contributes to impaired cardiac energy levels, increased reactive oxygen species production, cardiomyocyte apoptosis and the decline in cardiac function...
March 2, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28246204/science-signaling-podcast-for-28-february-2017-balancing-autophagy-in-the-stressed-heart
#17
Saumya Das, Annalisa M VanHook
This Podcast features an interview with Saumya Das, senior author of a Research Article that appears in the 28 February 2017 issue of Science Signaling, about a protein that inhibits pathological cardiac hypertrophy in mice. Temporary increases in cardiac workload, such as those caused by exercise or pregnancy, induce physiological cardiac hypertrophy, a beneficial type of heart enlargement that is adaptive. However, a sustained increase in workload due to metabolic stress or uncontrolled high blood pressure induces pathological cardiac hypertrophy, which can contribute to heart failure...
February 28, 2017: Science Signaling
https://www.readbyqxmd.com/read/28246202/ddit4l-promotes-autophagy-and-inhibits-pathological-cardiac-hypertrophy-in-response-to-stress
#18
Bridget Simonson, Vinita Subramanya, Mun Chun Chan, Aifeng Zhang, Hannabeth Franchino, Filomena Ottaviano, Manoj K Mishra, Ashley C Knight, Danielle Hunt, Ionita Ghiran, Tejvir S Khurana, Maria I Kontaridis, Anthony Rosenzweig, Saumya Das
Physiological cardiac hypertrophy, in response to stimuli such as exercise, is considered adaptive and beneficial. In contrast, pathological cardiac hypertrophy that arises in response to pathological stimuli such as unrestrained high blood pressure and oxidative or metabolic stress is maladaptive and may precede heart failure. We found that the transcript encoding DNA damage-inducible transcript 4-like (DDiT4L) was expressed in murine models of pathological cardiac hypertrophy but not in those of physiological cardiac hypertrophy...
February 28, 2017: Science Signaling
https://www.readbyqxmd.com/read/28237394/developmental-changes-in-the-balance-of-glycolytic-atp-production-and-oxidative-phosphorylation-in-ventricular-cells-a-simulation-study
#19
Hitomi I Sano, Tamami Toki, Yasuhiro Naito, Masaru Tomita
The developmental program of the heart requires accurate regulation to ensure continuous circulation and simultaneous cardiac morphogenesis, because any functional abnormalities may progress to congenital heart malformation. Notably, energy metabolism in fetal ventricular cells is regulated in a manner that differs from adult ventricular cells: fetal cardiomyocytes generally have immature mitochondria and fetal ventricular cells show greater dependence on glycolytic ATP production. However, although various characteristics of energy metabolism in fetal ventricular cells have been reported, to our knowledge, a quantitative description of the contributions of these factors to fetal ventricular cell functions has not yet been established...
February 24, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28230173/a-novel-physiological-role-for-cardiac-myoglobin-in-lipid-metabolism
#20
Ulrike B Hendgen-Cotta, Sonja Esfeld, Cristina Coman, Robert Ahrends, Ludger Klein-Hitpass, Ulrich Flögel, Tienush Rassaf, Matthias Totzeck
Continuous contractile activity of the heart is essential and the required energy is mostly provided by fatty acid (FA) oxidation. Myocardial lipid accumulation can lead to pathological responses, however the underlying mechanisms remain elusive. The role of myoglobin in dioxygen binding in cardiomyocytes and oxidative skeletal muscle has widely been appreciated. Our recent work established myoglobin as a protector of cardiac function in hypoxia and disease states. We here unravel a novel role of cardiac myoglobin in governing FA metabolism to ensure the physiological energy production through β-oxidation, preventing myocardial lipid accumulation and preserving cardiac functions...
February 23, 2017: Scientific Reports
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