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'carnitine' 'cardiac'

Keiko Ishigaki, Ikuko Kato, Terumi Murakami, Takatoshi Sato, Minobu Shichiji, Kumiko Ishiguro, Kiyonobu Ishizuka, Makoto Funatsuka, Kayoko Saito, Makiko Osawa, Satoru Nagata
BACKGROUND: The leading cause of death in patients with Fukuyama congenital muscular dystrophy (FCMD) is congestive heart failure or respiratory dysfunction, which is same as that in Duchenne muscular dystrophy (DMD). Recent studies reported that renal dysfunction is a common complication and an increasing cause of death in advanced DMD. It can be attributable to circulatory instability or inappropriate use of drugs for treating cardiac dysfunction. METHODS: We retrospectively evaluated renal function in 38 genetically diagnosed patients with FCMD (range, 1...
August 1, 2018: Brain & Development
Suprovath Kumar Sarker, Md Tarikul Islam, Golam Sarower Bhuyan, Nusrat Sultana, Mst Noorjahan Begum, Mohammad Al Mahmud-Un-Nabi, Md Abdulla Al Noman Howladar, Tashmim Farhana Dipta, A K M Muraduzzaman, Syeda Kashfi Qadri, Tahmina Shirin, Salma Sadiya, Manzoor Hussain, Waqar Ahmed Khan, Sharif Akhteruzzaman, Syed Saleheen Qadri, Firdausi Qadri, Kaiissar Mannoor
Patients with beta-thalassemia major (BTM) suffer from fatigue, poor physical fitness, muscle weakness, lethargy, and cardiac complications which are related to an energy crisis. Carnitine and acylcarnitine derivatives play important roles in fatty acid oxidation, and deregulation of carnitine and acylcarnitine metabolism may lead to an energy crisis. The present study aimed to investigate carnitine and acylcarnitine metabolites to gain an insight into the pathophysiology of BTM. Dried blood spots of 45 patients with BTM and 96 age-matched healthy controls were analyzed for free carnitine and 24 acylcarnitines by using liquid chromatography-tandem mass spectrometry (LC-MS/MS)...
July 2018: Journal of Advanced Research
Terumi Higuchi
BACKGROUND: Carnitine deficiency is a common condition in hemodialysis patients. There have been numerous reports on the efficacy of levocarnitine therapy in hemodialysis patients, including different views. Reported effects of levocarnitine are: (1) improvement of renal anemia, (2) improvement of cardiac functions, (3) effects on muscle spasm and asthenia, (4) anti-atherogenic effects, (5) anti-oxidant and anti-inflammatory effects, and (6) inhibitory effects on dialysis hypotension...
2018: Contributions to Nephrology
Yingxue Wang, Bridgette A Christopher, Kirkland A Wilson, Deborah Muoio, Robert W McGarrah, Henri Brunengraber, Guo-Fang Zhang
High concentrations of propionate and its metabolites are found in several diseases that are often associated with the development of cardiac dysfunction, such as obesity, diabetes, propionic acidemia, and methylmalonic acidemia. In the present work, we employed a stable isotope-based metabolic flux approach to understand propionate-mediated perturbation of cardiac energy metabolism. Propionate led to accumulation of propionyl-CoA (increased by ~101-fold) and methylmalonyl-CoA (increased by 36-fold). This accumulation caused significant mitochondrial CoA trapping and inhibited fatty acid oxidation...
July 17, 2018: American Journal of Physiology. Endocrinology and Metabolism
Andoni Echaniz-Laguna, Valérie Biancalana, Pauline Gaignard, Jean-Baptiste Chanson
Rhabdomyolysis is an emergency requiring rapid diagnosis and suitable aetiological treatment. We describe the case of a 57-year-old man with recurrent exertional rhabdomyolysis who was diagnosed with systemic primary carnitine deficiency (SPCD). Clinical examination was normal, creatine kinase levels were elevated, plasma free carnitine concentration was mildly decreased, muscle biopsy demonstrated lipid accumulation, carnitine uptake in cultured fibroblasts was decreased and genetic analysis identified a homozygous pathologic c...
June 11, 2018: BMJ Case Reports
Neda Ranjbar Kohan, Saeed Nazifi, Mohammad Reza Tabandeh, Maryam Ansari Lari
Objective: L-carnitine (LC) has been shown to protect cardiac metabolism in diabetes patients with cardiovascular diseases (CVDs). Apelin, a newly discovered adipocytokines, is an important regulator of cardiac muscle function; however, the role of the level of expression of Apelin axis in improvement of cardiac function by LC in diabetic patients, is not clear. In the present study, obese insulin-resistant rats were used to determine the effect of LC, when given orally with a high-calorie diet, on Apelin and Apelin receptor (Apj) expression in cardiac muscle...
October 2018: Cell Journal
Angela S Koh, Fei Gao, Shuang Leng, Jean-Paul Kovalik, Xiaodan Zhao, Ru San Tan, Kevin Timothy Fridianto, Jianhong Ching, Serene Jm Chua, Jian-Min Yuan, Woon-Puay Koh, Liang Zhong
Among community cohorts, associations between clinical and metabolite factors and complex left atrial (LA) phasic function assessed by cardiac magnetic resonance (CMR) feature tracking (FT) are unknown. Longitudinal LA strain comprising reservoir strain (εs), conduit strain (εe) and booster strain (εa) and their corresponding peak strain rates (SRs, SRe, SRa) were measured using CMR FT. Targeted mass spectrometry measured 83 circulating metabolites in serum. Sparse Principal Component Analysis was used for data reduction...
May 25, 2018: Scientific Reports
Na Lv, Meng Zhao, Yantao Han, Lianhua Cui, Weizhen Zhong, Chunbo Wang, Qixiao Jiang
Perfluorooctanoic acid (PFOA), a wide spread environmental pollutant, was associated with developmental cardiotoxicity in chicken embryo, while the underlying molecular mechanism had not been fully elucidated. In the current study, 2 mg/kg (egg weight) PFOA and/or 100 mg/kg (egg weight) l-carnitine were exposed to embryonic day zero (ED0) chicken embryo via air cell injection, and then bone morphogenic protein 2 (BMP2) silencing lentivirus or BMP2 recombinant protein were introduced into ED2 embryo. Electrocardiography and histological methods were utilized to assess the cardiac function and morphology in hatchling chickens, respectively...
August 1, 2018: Toxicology and Applied Pharmacology
Ilknur Kulhas Celik, Haydar Ali Tasdemir, Hülya Ince, Halil Celik, Metin Sungur
OBJECTIVES: In the study, the effect of valproic acid on serum free/acylcarnitine levels and left ventricular systolic function in pediatric patients with idiopathic epilepsy receiving valproic acid was investigated. PATIENTS AND METHODS: Patients receiving valproic acid treatment for six months between January 2012 and December 2012 were evaluated. Blood samples were obtained from the participants twice (pretreatment and the sixth month of treatment) and serum-free and acylcarnitine levels (from C2 to C18:1-OH) were measured using tandem mass spectrometry...
July 2018: Clinical Neurology and Neurosurgery
Patrick Rockenfeller, Campbell W Gourlay
Lipotoxicity is a pathophysiological process triggered by lipid overload. In metazoans, lipotoxicity is characterised by the ectopic deposition of lipids on organs other than adipose tissue. This leads to organ dysfunction, cell death, and is intimately linked to lipid-associated diseases such as cardiac dysfunction, atherosclerosis, stroke, hepatosteatosis, cancer and the metabolic syndrome. The molecules involved in eliciting lipotoxicity include FAs and their acyl-CoA derivatives, triacylglycerol (TG), diacylglycerol (DG), ceramides, acyl-carnitines and phospholipids...
June 1, 2018: FEMS Yeast Research
M Marcinkiewicz-Siemion, M Ciborowski, K Ptaszynska-Kopczynska, A Szpakowicz, A Lisowska, M Jasiewicz, E Waszkiewicz, A Kretowski, W J Musial, K A Kaminski
Cardiac and extracardiac lipid metabolism is known to be significantly altered in the course of the heart failure with reduced ejection fraction (HF-REF), however the precise mechanisms are not fully elucidated. The aim of the study was to use of untargeted metabolomics to identify and validate changes in the blood metabolites profile, occurring as a result of HF-REF development. The analyses were performed first in the derivation set (36 chronic HF-REF patients and 19 controls without the disease) and repeated in validation cohort (31 chronic HF-REF patients and 20 controls)...
May 30, 2018: Journal of Pharmaceutical and Biomedical Analysis
Nam Nhut Phan, Kuan-Lun Li, Yen-Chang Lin
BACKGROUND: Arsenic has been shown to cause various diseases (such as blackfoot disease, cardiovascular diseases, bladder cancer and skin cancer) in many areas of the world. However, the effects of arsenic on cardiac rhythm functions still lack investigation. METHODS: In this study, different concentrations of arsenic were orally applied to Sprague Dawley rats in order to examine the relationship between arsenic and cardiovascular rhythm (i.e. long QT) via electrocardiography measurement...
July 2018: Toxicology Mechanisms and Methods
Robert M Gill, Marisa O'Brien, Adrian Young, Danielle Gardiner, Ryan J Mailloux
Protein S-glutathionylation is a reversible redox modification that regulates mitochondrial metabolism and reactive oxygen species (ROS) production in liver and cardiac tissue. However, whether or not it controls ROS release from skeletal muscle mitochondria has not been explored. In the present study, we examined if chemically-induced protein S-glutathionylation could alter superoxide (O2●-)/hydrogen peroxide (H2O2) release from isolated muscle mitochondria. Disulfiram, a powerful chemical S-glutathionylation catalyst, was used to S-glutathionylate mitochondrial proteins and ascertain if it can alter ROS production...
2018: PloS One
Tariq R Altamimi, Panakkezhum D Thomas, Ahmed M Darwesh, Natasha Fillmore, Mohammad U Mahmoud, Liyan Zhang, Abhishek Gupta, Rami Al Batran, John M Seubert, Gary D Lopaschuk
The role of carnitine acetyltransferase (CrAT) in regulating cardiac energy metabolism is poorly understood. CrAT modulates mitochondrial acetyl-CoA/CoA (coenzyme A) ratios, thus regulating pyruvate dehydrogenase activity and glucose oxidation. Here, we propose that cardiac CrAT also provides cytosolic acetyl-CoA for the production of malonyl-CoA, a potent inhibitor of fatty acid oxidation. We show that in the murine cardiomyocyte cytosol, reverse CrAT activity (RCrAT, producing acetyl-CoA) is higher compared with the liver, which primarily uses ATP-citrate lyase to produce cytosolic acetyl-CoA for lipogenesis...
March 9, 2018: Biochemical Journal
Jianhua Xiong, Hiroyuki Kawagishi, Ye Yan, Jie Liu, Quinn S Wells, Lia R Edmunds, Maria M Fergusson, Zu-Xi Yu, Ilsa I Rovira, Evan L Brittain, Michael J Wolfgang, Michael J Jurczak, Joshua P Fessel, Toren Finkel
Endothelial-to-mesenchymal transition (EndoMT) is a cellular process often initiated by the transforming growth factor β (TGF-β) family of ligands. Although required for normal heart valve development, deregulated EndoMT is linked to a wide range of pathological conditions. Here, we demonstrate that endothelial fatty acid oxidation (FAO) is a critical in vitro and in vivo regulator of EndoMT. We further show that this FAO-dependent metabolic regulation of EndoMT occurs through alterations in intracellular acetyl-CoA levels...
February 15, 2018: Molecular Cell
Keiki Sugi, Paishiun N Hsieh, Olga Ilkayeva, Shamanthika Shelkay, Bridget Moroney, Palvir Baadh, Browning Haynes, Megan Pophal, Liyan Fan, Christopher B Newgard, Domenick A Prosdocimo, Mukesh K Jain
Cardiac metabolism is highly adaptive in response to changes in substrate availability, as occur during fasting. This metabolic flexibility is essential to the maintenance of contractile function and is under the control of a group of select transcriptional regulators, notably the nuclear receptor family of factors member PPARα. However, the diversity of physiologic and pathologic states through which the heart must sustain function suggests the possible existence of additional transcriptional regulators that play a role in matching cardiac metabolism to energetic demand...
2018: PloS One
Aneesh Karkhanis, Jacqueline Wen Hui Leow, Thilo Hagen, Eric Chun Yong Chan
Dronedarone and amiodarone are structurally similar antiarrhythmic drugs. Dronedarone worsens cardiac adverse effects with unknown causes while amiodarone has no cardiac adversity. Dronedarone induces preclinical mitochondrial toxicity in rat liver and exhibits clinical hepatotoxicity. Here, we further investigated the relative potential of the antiarrhythmic drugs in causing mitochondrial injury in cardiomyocytes. Differentiated rat H9c2 cardiomyocytes were treated with dronedarone, amiodarone, and their respective metabolites namely N-desbutyldronedarone (NDBD) and N-desethylamiodarone (NDEA)...
May 1, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Gema Marín-Royo, Isabel Gallardo, Ernesto Martínez-Martínez, Beatriz Gutiérrez, Raquel Jurado-López, Natalia López-Andrés, Josué Gutiérrez-Tenorio, Eduardo Rial, Marı A Visitación Bartolomé, María Luisa Nieto, Victoria Cachofeiro
Obesity is accompanied by metabolic alterations characterized by insulin resistance and cardiac lipotoxicity. Galectin-3 (Gal-3) induces cardiac inflammation and fibrosis in the context of obesity; however, its role in the metabolic consequences of obesity is not totally established. We have investigated the potential role of Gal-3 in the cardiac metabolic disturbances associated with obesity. In addition, we have explored whether this participation is, at least partially, acting on mitochondrial damage. Gal-3 inhibition in rats that were fed a high-fat diet (HFD) for 6 weeks with modified citrus pectin (MCP; 100 mg/kg/day) attenuated the increase in cardiac levels of total triglyceride (TG)...
February 5, 2018: Disease Models & Mechanisms
Victoria A Serhiyenko, Alexandr A Serhiyenko
Cardiac autonomic neuropathy (CAN) is a serious complication of diabetes mellitus (DM) that is strongly associated with approximately five-fold increased risk of cardiovascular mortality. CAN manifests in a spectrum of things, ranging from resting tachycardia and fixed heart rate (HR) to development of "silent" myocardial infarction. Clinical correlates or risk markers for CAN are age, DM duration, glycemic control, hypertension, and dyslipidemia (DLP), development of other microvascular complications...
January 15, 2018: World Journal of Diabetes
Y J Pan, F P Lu
Objective: To investigate the effect of intravenous supplementation with high-dose L-carnitinen on hemodialysis tolerance in uremic patients with severe heart disease (ischemic heart disease, congestive heart disease and arrhythmia). Methods: Between March 2012 and March 2017, 5 gram L-carnitine was given after the completion of each hemodialysis treatment (3-4 times a week) over a period of two weeks in 29 maintenance hemodialysis patients with severe heart diseases manifested by frequently symptomatic hypotension, chest tightness, wheezing, palpitation, chest pain and other symptoms during hemodialysis...
December 26, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
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