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L-carnitine and cardiomyocytes

Kensuke Tsushima, Heiko Bugger, Adam R Wende, Jamie Soto, Gregory A Jenson, Austin R Tor, Rose McGlauflin, Helena C Kenny, Yuan Zhang, Rhonda Souvenir, Xiao X Hu, Crystal L Sloan, Renata O Pereira, Vitor A Lira, Kenneth W Spitzer, Terry L Sharp, Kooresh I Shoghi, Genevieve C Sparagna, Eva A Rog-Zielinska, Peter Kohl, Oleh Khalimonchuk, Jean E Schaffer, E Dale Abel
RATIONALE: Cardiac lipotoxicity, characterized by increased uptake, oxidation, and accumulation of lipid intermediates, contributes to cardiac dysfunction in obesity and diabetes mellitus. However, mechanisms linking lipid overload and mitochondrial dysfunction are incompletely understood. OBJECTIVE: To elucidate the mechanisms for mitochondrial adaptations to lipid overload in postnatal hearts in vivo. METHODS AND RESULTS: Using a transgenic mouse model of cardiac lipotoxicity overexpressing ACSL1 (long-chain acyl-CoA synthetase 1) in cardiomyocytes, we show that modestly increased myocardial fatty acid uptake leads to mitochondrial structural remodeling with significant reduction in minimum diameter...
January 5, 2018: Circulation Research
Mei Xue, Xu Chen, Zhija Guo, Xiaoqian Liu, Yanping Bi, Jie Yin, Haiyan Hu, Ping Zhu, Jian Zhuang, Courtney Cates, Thomas Rousselle, Ji Li
We aim to investigate the cardioprotective effects of L-carnitine (LC) on cardiac function during ischemia and reperfusion (I/R) and contractile function of single cardiomyocyte. C57BL/6 J mice were randomly assigned to 5 groups: sham group; vehicle group, LC preconditioning group, LC preconditioning + LY294002 (a PI3K/Akt signaling pathway inhibitor) group (LC + LY), and LY294002 group (LY). The sham group was exposed to the open heart operation but not I/R, the other groups received 45 min ischemia/48 h reperfusion...
December 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
Su-Ying Wen, Bharath Kumar Velmurugan, Cecilia Hsuan Day, Chia-Yao Shen, Li-Chin Chun, Yi-Chieh Tsai, Yueh-Min Lin, Ray-Jade Chen, Chia-Hua Kuo, Chih-Yang Huang
In our previous study palmitic acid (PA) induced lipotoxicity and switches energy metabolism from CD36 to GLUT4 in H9c2 cells. Low level of high density lipoprotein (HDL) is an independent risk factor for cardiac hypertrophy. Therefore, we in the present study investigated whether HDL can reverse PA induced lipotoxicity in H9c2 cardiomyoblast cells. In this study, we treated H9c2 cells with PA to create a hyperlipidemia model in vitro and analyzed for CD36 and GLUT4 metabolic pathway proteins. CD36 metabolic pathway proteins (phospho-AMPK, SIRT1, PGC1α, PPARα, CPT1β, and CD36) were decreased by high PA (150 and 200 μg/μl) concentration...
November 2017: Journal of Cellular Physiology
Sheila da Silva Guimarães, Wanise de Souza Cruz, Licinio da Silva, Gabrielle Maciel, Ana Beatriz Huguenin, Monicque de Carvalho, Bárbara Costa, Geisiane da Silva, Carlos da Costa, João Alvaro D'Ippolito, Alexandre Colafranceschi, Fernanda Scalco, Gilson Boaventura
During cardiac failure, cardiomyocytes have difficulty in using the substrates to produce energy. L-carnitine is a necessary nutrient for the transport of fatty acids that are required for generating energy. Coronary artery graft surgery reduces the plasma levels of L-carnitine and increases the oxidative stress. This study demonstrates the effect of L-carnitine supplementation on the reverse remodeling of patients undergoing coronary artery bypass graft. Patients with ischemic heart failure who underwent coronary graft surgery were randomized to group A - supplemented with L-carnitine or group B controls...
2017: Annals of Nutrition & Metabolism
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
Aizhu Li, Xuejun Guo, Jiabin Xie, Xinyu Liu, Zhenzhu Zhang, Yubo Li, Yanjun Zhang
Corex Periplocae (the root of Periploca sepium Bge) has been widely used in clinics. Periplocin, as one of the components of cardiac glycosides in Corex Periplocae, easily triggers cardiotoxicity when used improperly. To evaluate the toxicity of Periplocin, we used UPLC-Q-TOF/MS to investigate metabolic profiles on neonatal rat cardiomyocytes exposed to high and low doses of Periplocin (0.2 mmol/L, 0.4 mmol/L). Finally, we identified 11 biomarkers associated with toxicity through multivariate statistical analysis...
May 10, 2016: Journal of Pharmaceutical and Biomedical Analysis
Amir Baghaei, Reza Solgi, Abbas Jafari, Amir Hossein Abdolghaffari, Alireza Golaghaei, Mohammad Hossein Asghari, Maryam Baeeri, Seyed Nasser Ostad, Mohammad Sharifzadeh, Mohammad Abdollahi
The aim of the present study was to investigate the efficacy of acetyl-L-carnitine (ALCAR) on pathologic changes of mitochondrial respiratory chain activity, ATP production, oxidative stress, and cellular apoptosis/necrosis induced by aluminum phosphide (AlP) poisoning. The study groups included: the Sham that received almond oil only; the AlP that received oral LD50 dose of aluminum; the AC-100, AC-200, and AC-300 which received concurrent oral LD50 dose of AlP and single 100, 200, and 300 mg/kg of ALCAR by intraperitoneal injection...
March 2016: Environmental Toxicology and Pharmacology
Antonio J Blanca, María V Ruiz-Armenta, Sonia Zambrano, José L Miguel-Carrasco, José L Arias, Miguel Arévalo, Alfonso Mate, Oscar Aramburu, Carmen M Vázquez
Sunitinib (Su) is currently approved for treatment of several malignances. However, along with the benefits of disease stabilization, cardiovascular toxicities have also been increasingly recognized. The aim of this study was to analyze which mechanisms are involved in the cardiotoxicity caused by Su, as well as to explore the potential cardioprotective effects of l-carnitine (LC). To this end, four groups of Wistar rats were used: (1) control; (2) rats treated with 400mg LC/kg/day; (3) rats treated with 25mg Su/kg/day; and (4) rats treated with LC+Su simultaneously...
January 22, 2016: Toxicology Letters
Eri Oyanagi, Masataka Uchida, Takeshi Miyakawa, Motohiko Miyachi, Hidetaka Yamaguchi, Kuniatsu Nagami, Kozo Utsumi, Hiromi Yano
Although palmitoleic acid (C16:1) is associated with arrhythmias, and increases in an age-dependent matter, the effects of L-carnitine, which is essential for the transport of long-chain fatty acids into the mitochondria, are unclear. It has been postulated that L-carnitine may attenuate palmitate (C16:0)-induced mitochondrial dysfunction and the apoptosis of cardiomyocytes. The aim of this study was to elucidate the activity of L-carnitine in the prevention of the palmitoleic acid-induced mitochondrial membrane permeability transition and cytochrome c release using isolated cardiac mitochondria from rats...
July 17, 2015: Biochemical and Biophysical Research Communications
Kai Lu, Guanglei Chang, Lin Ye, Peng Zhang, Yong Li, Dongying Zhang
Glucagon-like peptide-1 (GLP-1) analogues are likely to exert cardioprotective effects via balancing the energy metabolism in cardiomyocytes following ischemic or hypoxic insults. The present study aimed to explore the protective effects and mechanism of exendin-4, a GLP-1 analogue, on cardiomyocyte glucose uptake using an in vitro model of hypoxia/reoxygenation (H/R) of H9c2 cardiomyocyte cells. Pre-treatment with exendin-4 (200 nM) prior to H/R increased the cell viability, decreased cell apoptosis, enhanced cardiomyocyte glucose uptake and increased the production of adenosine triphosphate...
August 2015: Molecular Medicine Reports
Aly Elezaby, Aaron L Sverdlov, Vivian H Tu, Kanupriya Soni, Ivan Luptak, Fuzhong Qin, Marc Liesa, Orian S Shirihai, Jamie Rimer, Jean E Schaffer, Wilson S Colucci, Edward J Miller
BACKGROUND: Obesity leads to metabolic heart disease (MHD) that is associated with a pathologic increase in myocardial fatty acid (FA) uptake and impairment of mitochondrial function. The mechanism of mitochondrial dysfunction in MHD, which results in oxidant production and decreased energetics, is poorly understood but may be related to excess FAs. Determining the effects of cardiac FA excess on mitochondria can be hindered by the systemic sequelae of obesity. Mice with cardiomyocyte-specific overexpression of the fatty acid transport protein FATP1 have increased cardiomyocyte FA uptake and develop MHD in the absence of systemic lipotoxicity, obesity or diabetes...
February 2015: Journal of Molecular and Cellular Cardiology
Junfang Wu, Jie Niu, Xiaopeng Li, Xianwei Wang, Zhikun Guo, Fenxi Zhang
BACKGROUND: Bone marrow derived mesenchymal stem cells (bmMSCs) are multipotent cells that can differentiate into diverse cell types, including cardiomyocytes. BmMSC-based transplantation is capable of repairing acute and chronic myocardial infarction. Prior to the transplantation, MSCs are usually induced in vitro by biological reagents and chemicals for directional differentiation. Transforming growth factor beta (TGF-β) is one of the most commonly used biological reagents for induction of cardiomyocyte differentiation of bmMSCs...
May 18, 2014: BMC Developmental Biology
Makiko Miyata, Akiomi Yoshihisa, Hiroyuki Yamauchi, Takashi Owada, Takamasa Sato, Satoshi Suzuki, Koichi Sugimoto, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Hitoshi Suzuki, Shu-Ichi Saitoh, Yasuchika Takeishi
Sleep-disordered breathing (SDB) has a critical association with mortality and morbidity of patients with chronic heart failure (CHF). Troponin T is a marker of ongoing myocardial damage and predicts adverse clinical outcomes in patients with CHF. Carnitine plays an important role in the utilization of fatty acids in the myocardium. It has been reported that myocardial carnitine levels decrease in the failing heart. We hypothesized that plasma troponin T and carnitine are increased due to the leakage from damaged cardiomyocytes or the alteration of myocardial metabolism in CHF patients with SDB...
May 2015: Heart and Vessels
Shervi Lie, Melisa Hui, I Caroline McMillen, Beverly S Muhlhausler, Giuseppe S Posterino, Stacey L Dunn, Kimberley C Wang, Kimberley J Botting, Janna L Morrison
It is unknown whether cardiomyocyte hypertrophy and the transition to fatty acid oxidation as the main source of energy after birth is dependent on the maturation of the cardiomyocytes' metabolic system, or on the limitation of substrate availability before birth. This study aimed to investigate whether intrafetal administration of a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, rosiglitazone, during late gestation can stimulate the expression of factors regulating cardiac growth and metabolism in preparation for birth, and the consequences of cardiac contractility in the fetal sheep at ∼140 days gestation...
March 15, 2014: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Marta Stadnik, Gabriela Handzlik-Orlik, Kamil Sarnecki, Robert Krysiak, Bogusław Okopień
Trimetazidine, next to ranolazine and L-carnitine, belongs to cardioprotective drugs and as their main agent is used in experimental and clinical trials to evaluate its effect on modulation of cardiomyocytes metabolism. The blockade of fatty acid oxidation in ischemic myocardium and increase in the glucose utilization are the main mechanisms of trimetazidine action, which eventually lead to the reduction in intracellular acidosis. Recent studies concerning cardioprotective treatment encourage to continue the research on effectiveness, possible side effects, and clinical outcome which arise from "metabolic shift" toward the improvement of glucose metabolism...
2013: Przegla̧d Lekarski
Lars Hoffmann, Annette Seibt, Diran Herebian, Ute Spiekerkoetter
Patients with inborn errors of long-chain fatty acid oxidation accumulate disease-specific acylcarnitines and triacylglycerols in various tissues. Some of these patients present significant cardiac diseases such as arrhythmias and cardiomyopathy. The mechanism of how fatty acid accumulation is involved in disease pathogenesis is still unclear but apoptosis of cardiomyocytes has been suggested to be one possible mechanism of cardiomyopathy development. In this study, we measured lipid uptake and intracellular lipid accumulation after incubation of HL1 cardiomyocytes with different saturated and monounsaturated long- and medium-chain fatty acid species for various time periods and at different physiological concentrations...
January 2014: Lipids
Feng Zhou, Wen Zhong, Jie Xue, Zhen-lun Gu, Mei-lin Xie
The objective of this study was to examine the therapeutic effect of osthol, a coumarin compound isolated from the fruit of Cnidium monnieri (L.) Cusson, on cardiac hypertrophy in rats and investigate its potential mechanisms. The rats with cardiac hypertrophy induced by renovascular hypertension were given osthol orally by gavage for 4 weeks. The results showed that in the osthol 20 mg/kg group, the blood pressure, heart weight index and myocardial malondialdehyde content were lowered (p < 0.001, p = 0...
October 2012: Lipids
Hsiang-Po Huang, Pin-Hsun Chen, Wuh-Liang Hwu, Ching-Yu Chuang, Yin-Hsiu Chien, Lee Stone, Chung-Liang Chien, Li-Tzu Li, Shu-Chuan Chiang, Hsin-Fu Chen, Hong-Nerng Ho, Chung-Hsuan Chen, Hung-Chih Kuo
Pompe disease is caused by autosomal recessive mutations in the acid alpha-glucosidase (GAA) gene, which encodes GAA. Although enzyme replacement therapy has recently improved patient survival greatly, the results in skeletal muscles and for advanced disease are still not satisfactory. Here, we report the derivation of Pompe disease-induced pluripotent stem cells (PomD-iPSCs) from two patients with different GAA mutations and their potential for pathogenesis modeling, drug testing and disease marker identification...
December 15, 2011: Human Molecular Genetics
Markus Grube, Sabine Ameling, Michel Noutsias, Kathleen Köck, Ivonne Triebel, Karina Bonitz, Konrad Meissner, Gabriele Jedlitschky, Lars R Herda, Markus Reinthaler, Maria Rohde, Wolfgang Hoffmann, Uwe Kühl, Heinz-Peter Schultheiss, Uwe Völker, Stephan B Felix, Karin Klingel, Reinhard Kandolf, Heyo K Kroemer
Organic cation transporters (OCT1-3 and OCTN1/2) facilitate cardiac uptake of endogenous compounds and numerous drugs. Genetic variants of OCTN2, for example, reduce uptake of carnitine, leading to heart failure. Whether expression and function of OCTs and OCTNs are altered by disease has not been explored in detail. We therefore studied cardiac expression, heart failure-dependent regulation, and affinity to cardiovascular drugs of these transporters. Cardiac transporter mRNA levels were OCTN2>OCT3>OCTN1>OCT1 (OCT2 was not detected)...
June 2011: American Journal of Pathology
Hung-Hsin Chao, Ju-Chi Liu, Hong-Jye Hong, Jia-wei Lin, Cheng-Hsien Chen, Tzu-Hurng Cheng
BACKGROUND: Clinical use of doxorubicin is greatly limited by its severe cardiotoxic side effects. L-carnitine is a vitamin-like substance which has been successfully used in many cardiomyopathies, however, the intracellular mechanism(s) remain unclear. The objective of this study was set to evaluate the protective effect of L-carnitine on doxorubicin-induced cardiomyocyte apoptosis, and to explore its intracellular mechanism(s). METHODS: Primary cultured neonatal rat cardiomyocytes were treated with doxorubicin (1 µM) with or without pretreatment with L-carnitine (1-30 mM)...
January 21, 2011: International Journal of Cardiology
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