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cardiomyocyte and metabolism

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https://www.readbyqxmd.com/read/28532817/-pro-renin-receptor-as-a-therapeutic-target-for-the-treatment-of-cardiovascular-diseases
#1
REVIEW
Yuan Sun, A H Jan Danser, Xifeng Lu
The discovery of the (pro)renin receptor [(P)RR] 15years ago stimulated ideas on prorenin being more than renin's inactive precursor. Indeed, binding of prorenin to the (P)RR induces a conformational change in the prorenin molecule, allowing it to display angiotensin-generating activity, and additionally results in intracellular signaling in an angiotensin-independent manner. However, the prorenin levels required to observe these angiotensin-dependent and -independent effects of the (P)RR are many orders above its in vivo concentrations, both under normal and pathological conditions...
May 19, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28526246/impaired-mitophagy-facilitates-mitochondrial-damage-in-danon-disease
#2
Sherin I Hashem, Anne N Murphy, Ajit S Divakaruni, Matthew L Klos, Bradley C Nelson, Emily C Gault, Teisha J Rowland, Cynthia N Perry, Yusu Gu, Nancy D Dalton, William H Bradford, Eric J Devaney, Kirk L Peterson, Kenneth L Jones, Matthew R G Taylor, Ju Chen, Neil C Chi, Eric D Adler
RATIONALE: Lysosomal associated membrane protein type-2 (LAMP-2) is a highly conserved, ubiquitous protein that is critical for autophagic flux. Loss of function mutations in the LAMP-2 gene cause Danon disease, a rare X-linked disorder characterized by developmental delay, skeletal muscle weakness, and severe cardiomyopathy. We previously found that human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from Danon patients exhibited significant mitochondrial oxidative stress and apoptosis...
May 16, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28515362/insulin-supplementation-attenuates-cancer-induced-cardiomyopathy-and-slows-tumor-disease-progression
#3
James T Thackeray, Stefan Pietzsch, Britta Stapel, Melanie Ricke-Hoch, Chun-Wei Lee, Jens P Bankstahl, Michaela Scherr, Jörg Heineke, Gesine Scharf, Arash Haghikia, Frank M Bengel, Denise Hilfiker-Kleiner
Advanced cancer induces fundamental changes in metabolism and promotes cardiac atrophy and heart failure. We discovered systemic insulin deficiency in cachectic cancer patients. Similarly, mice with advanced B16F10 melanoma (B16F10-TM) or colon 26 carcinoma (C26-TM) displayed decreased systemic insulin associated with marked cardiac atrophy, metabolic impairment, and function. B16F10 and C26 tumors decrease systemic insulin via high glucose consumption, lowering pancreatic insulin production and producing insulin-degrading enzyme...
May 18, 2017: JCI Insight
https://www.readbyqxmd.com/read/28514664/lack-of-mttp-activity-in-pluripotent-stem-cell-derived-hepatocytes-and-cardiomyocytes-abolishes-apob-secretion-and-increases-cell-stress
#4
Ying Liu, Donna M Conlon, Xin Bi, Katherine J Slovik, Jianting Shi, Hailey I Edelstein, John S Millar, Ali Javaheri, Marina Cuchel, Evanthia E Pashos, Jahangir Iqbal, M Mahmood Hussain, Robert A Hegele, Wenli Yang, Stephen A Duncan, Daniel J Rader, Edward E Morrisey
Abetalipoproteinemia (ABL) is an inherited disorder of lipoprotein metabolism resulting from mutations in microsomal triglyceride transfer protein (MTTP). In addition to expression in the liver and intestine, MTTP is expressed in cardiomyocytes, and cardiomyopathy has been reported in several ABL cases. Using induced pluripotent stem cells (iPSCs) generated from an ABL patient homozygous for a missense mutation (MTTP(R46G)), we show that human hepatocytes and cardiomyocytes exhibit defects associated with ABL disease, including loss of apolipoprotein B (apoB) secretion and intracellular accumulation of lipids...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28513986/pleiotropic-effects-of-chronic-phorbol-ester-treatment-to-improve-glucose-transport-in-insulin-resistant-cardiomyocytes
#5
Christelle Viglino, Bahareh Khoramdin, Guillaume Praplan, Christophe Montessuit
Stimulation of glucose transport is an important determinant of myocardial susceptibility to ischemia and reperfusion. Stimulation of glucose transport is markedly impaired in cardiomyocytes exposed to free fatty acids (FFA). Deactivation of the Focal Adhesion Kinase (FAK) by FFA contributes to glucose transport impairment, and could be corrected by chronic treatment with the phorbol ester TPA. However, TPA must have effects in addition to FAK reactivation to restore stimulated glucose transport. Chronic treatment with TPA improved basal and stimulated glucose transport in FFA-exposed, but not in control cardiomyocytes...
May 17, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28509371/quantitative-assessment-of-sialo-glycoproteins-and-n-glycans-during-cardiomyogenic-differentiation-of-human-induced-pluripotent-stem-cells
#6
Sarah Anna Konze, Samanta Cajic, Astrid Oberbeck, René Hennig, Andreas Pich, Erdmann Rapp, Falk Buettner
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) may be used in regenerative medicine for individualized tissue transplants in future. For application in patients, the generated CMs have to be highly pure and well characterized. To overcome the prevalent scarcity of CM-specific markers, we quantitatively assessed cell surface exposed sialo-glycoproteins and N-glycans of hiPSCs, CM progenitors and CMs derived thereof. Applying a combination of metabolic labeling and specific sialo-glycoprotein capture, we could highly enrich and quantify membrane proteins during cardiomyogenic differentiation...
May 16, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28500736/high-density-lipoprotein-hdl-reverses-palmitic-acid-induced-energy-metabolism-imbalance-by-switching-cd36-and-glut4-signaling-pathways-in-cardiomyocyte
#7
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...
May 13, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28498888/cardiomyocyte-specific-loss-of-mitochondrial-p32-c1qbp-causes-cardiomyopathy-and-activates-stress-responses
#8
Toshiro Saito, Takeshi Uchiumi, Mikako Yagi, Rie Amamoto, Daiki Setoyama, Yuichi Matsushima, Dongchon Kang
Aims: Mitochondria are important organelles, dedicated to energy production. Mitochondrial p32/C1qbp, which functions as an RNA and protein chaperone, interacts with mitochondrial mRNA and is indispensable for mitochondrial function through its regulation of mitochondrial translation in cultured cell lines. However, the precise role of p32/C1qbp in vivo is poorly understood because of embryonic lethality in the systemic p32-deficient mouse. The goal of this study was to examine the physiological function of mitochondrial p32/C1qbp in the heart...
May 11, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28498411/mitochondrial-activity-and-oxidative-stress-functions-are-influenced-by-the-activation-of-ahr-induced-cyp1a1-overexpression-in-cardiomyocytes
#9
Bing Zhou, Xi Wang, Feng Li, Yingting Wang, Lei Yang, Xiaolong Zhen, Wuhong Tan
There is an endemic cardiomyopathy currently occurring in China, termed, Keshan disease (KD). The authors previously compared mitochondrial‑associated gene expression profiles of peripheral blood mononuclear cells (PBMCs) derived from KD patients and normal controls, using mitochondria‑focused cDNA microarray technology. The results detected an upregulation of the enzyme‑associated CYP1A1 gene, (ratios ≥2.0). The aryl hydrocarbon receptor (AhR) regulates the expression of numerous cytochrome P450 (CYP) genes including members of the CYP1 family; CYP1A1 and CYP1A2...
May 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28487965/ho-1-ebp-interaction-alleviates-cholesterol-induced-hypoxia-through-the-activation-of-the-akt-and-nrf2-mtor-pathways-and-inhibition-of-carbohydrate-metabolism-in-cardiomyocytes
#10
Xiaohan Jin, Zhongwei Xu, Jin Cao, Rui Yan, Ruicheng Xu, Ruiqiong Ran, Yongqiang Ma, Wei Cai, Rong Fan, Yan Zhang, Xin Zhou, Yuming Li
Heme oxygenase-1 (HO-1) is an inducible and cytoprotective enzyme that provides a defense against oxidant damage. The present study screened 137 HO-1/interacting proteins using a profound co-immunoprecipitation (Co-IP) coupled with proteomics, and profiled the global HO-1 interactome network, including oxidative phosphorylation, endoplasmic reticulum and transport vesicle functions. Among these molecules, we observed that a novel interactor, emopamil-binding protein (EBP), is closely related to the cholesterol metabolism process...
June 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28487363/modeling-oxygen-requirements-in-ischemic-cardiomyocytes
#11
Anthony D McDougal, C Forbes Dewey
Heart disease remains the leading cause of death globally. Although reperfusion following myocardial ischemia can prevent death by restoring nutrient flow, ischemia/reperfusion injury can cause significant heart damage. The mechanisms that drive ischemia/reperfusion injury are not well understood; currently, few methods can predict the state of the cardiac muscle cell and its metabolic conditions during ischemia. Here, we explored the energetic sustainability of cardiomyocytes, using a model for cellular metabolism to predict the levels of ATP following hypoxia...
May 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28473744/untargeted-metabolomics-reveals-a-mild-impact-of-remote-ischemic-conditioning-on-the-plasma-metabolome-and-%C3%AE-hydroxybutyrate-as-a-possible-cardioprotective-factor-and-biomarker-of-tissue-ischemia
#12
Mia Roest Laursen, Jakob Hansen, Casper Elkjær, Ninna Stavnager, Camilla Bak Nielsen, Kasper Pryds, Jacob Johnsen, Jan Møller Nielsen, Hans Erik Bøtker, Mogens Johannsen
INTRODUCTION: Remote ischemic conditioning (RIC) is a maneuver by which short non-lethal ischemic events are applied on distant organs or limbs to reduce ischemia and reperfusion injuries caused by e.g. myocardial infarct. Although intensively investigated, the specific mechanism of this protective phenomenon remains incompletely understood and in particular, knowledge on the role of small metabolites is scarce. OBJECTIVES: In this study, we aimed to study perturbations in the plasma metabolome following RIC and gain insight into metabolic changes by the intervention as well as to identify potential novel cardio-protective metabolites...
2017: Metabolomics: Official Journal of the Metabolomic Society
https://www.readbyqxmd.com/read/28473471/are-targeted-therapies-for-diabetic-cardiomyopathy-on-the-horizon
#13
REVIEW
Mitchel Tate, David J Grieve, Rebecca H Ritchie
Diabetes increases the risk of heart failure approximately 2.5-fold, independent of coronary artery disease and other comorbidities. This process, termed diabetic cardiomyopathy, is characterized by initial impairment of left ventricular (LV) relaxation followed by LV contractile dysfunction. Post-mortem examination reveals that human diastolic dysfunction is closely associated with LV damage, including cardiomyocyte hypertrophy, apoptosis and fibrosis, with impaired coronary microvascular perfusion. The pathophysiological mechanisms underpinning the characteristic features of diabetic cardiomyopathy remain poorly understood, although multiple factors including altered lipid metabolism, mitochondrial dysfunction, oxidative stress, endoplasmic reticulum (ER) stress, inflammation, as well as epigenetic changes, are implicated...
May 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28466688/the-role-of-peroxisome-proliferator-activated-receptor-%C3%AE-in-mediating-cardioprotection-against-ischemia-reperfusion-injury
#14
Chong-Bin Zhong, Xi Chen, Xu-Yue Zhou, Xian-Bao Wang
Myocardial infarction (MI) is a serious cardiovascular disease resulting in high rates of morbidity and mortality. Although advances have been made in restoring myocardial perfusion in ischemic areas, decreases in cardiomyocyte death and infarct size are still limited, attributing to myocardial ischemia/reperfusion (I/R) injury. It is necessary to develop therapies to restrict myocardial I/R injury and protect cardiomyocytes against further damage after MI. Many studies have suggested that peroxisome proliferator-activated receptor γ (PPARγ), a ligand-inducible nuclear receptor that predominantly regulates glucose and lipid metabolism, is a promising therapeutic target for ameliorating myocardial I/R injury...
January 1, 2017: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28459156/antioxidant-tempol-supresses-heart-cytosolic-phospholipase-a-sub-2-sub-%C3%AE-stimulated-by-chronic-intermittent-hypoxia
#15
Petra Micova, Martina Klevstig, Kristyna Holzerova, Marek Vecka, Jitka Zurmanova, Jan Neckar, Frantisek Kolar, Olga Novakova, Jiri Novotny, Marketa Hlavackova
Adaptation to chronic intermittent hypoxia (CIH) is associated with reactive oxygen species (ROS) generation implicated in the improved cardiac tolerance against acute ischemia/reperfusion injury. Phospholipases A<sub>2</sub> (PLA<sub>2</sub>s) play an important role in cardiomyocyte phospholipid metabolism influencing membrane homeostasis. Here we aimed to determine the effect of CIH (7000 m, 8h/day, 5 weeks) on the expression of cytosolic PLA<sub>2</sub> (cPLA<sub>2</sub>α), its phosphorylated form (p-cPLA<sub>2</sub>α), calcium-independent (iPLA<sub>2</sub>) and secretory (sPLA<sub>2</sub>IIA) at protein and mRNA levels as well fatty acids (FA) profile in left ventricular myocardium of adult male Wistar rats...
April 30, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28449778/histopathological-and-immunological-characteristics-of-tachycardia-induced-cardiomyopathy
#16
Karin A L Mueller, David Heinzmann, Karin Klingel, Petra Fallier-Becker, Reinhard Kandolf, Antonios Kilias, Britta Walker-Allgaier, Oliver Borst, Jörg Kumbrink, Thomas Kirchner, Harald Langer, Tobias Geisler, Jürgen Schreieck, Michael Gramlich, Meinrad Gawaz, Peter Seizer
BACKGROUND: Tachycardiomyopathy or tachycardia-induced cardiomyopathy (TCM) has been known for decades as a reversible form of nonischemic cardiomyopathy. However, its mechanism and properties remain poorly understood. OBJECTIVES: The current study investigated endomyocardial biopsy samples from patients with TCM and compared them with samples from patients with dilated cardiomyopathy (DCM) and inflammatory cardiomyopathy (ICM). METHODS: The study included 189 patients with new-onset heart failure and severely reduced ejection fraction not caused by valvular or ischemic heart disease...
May 2, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28445457/the-mitochondrial-na-ca-2-exchanger-is-essential-for-ca-2-homeostasis-and-viability
#17
Timothy S Luongo, Jonathan P Lambert, Polina Gross, Mary Nwokedi, Alyssa A Lombardi, Santhanam Shanmughapriya, April C Carpenter, Devin Kolmetzky, Erhe Gao, Jop H van Berlo, Emily J Tsai, Jeffery D Molkentin, Xiongwen Chen, Muniswamy Madesh, Steven R Houser, John W Elrod
Mitochondrial calcium (mCa(2+)) has a central role in both metabolic regulation and cell death signalling, however its role in homeostatic function and disease is controversial. Slc8b1 encodes the mitochondrial Na(+)/Ca(2+) exchanger (NCLX), which is proposed to be the primary mechanism for mCa(2+) extrusion in excitable cells. Here we show that tamoxifen-induced deletion of Slc8b1 in adult mouse hearts causes sudden death, with less than 13% of affected mice surviving after 14 days. Lethality correlated with severe myocardial dysfunction and fulminant heart failure...
May 4, 2017: Nature
https://www.readbyqxmd.com/read/28439717/negligible-effect-of-enos-palmitoylation-on-fatty-acid-regulation-of-contraction-in-ventricular-myocytes-from-healthy-and-hypertensive-rats
#18
Chun Li Jin, Yu Na Wu, Ji Hyun Jang, Zai Hao Zhao, Goo Taeg Oh, Sung Joon Kim, Yin Hua Zhang
S-palmitoylation is an important post-translational modification that affects the translocation and the activity of target proteins in a variety of cell types including cardiomyocytes. Since endothelial nitric oxide synthase (eNOS) is known to be palmitoylated and the activity of eNOS is essential in fatty acid-dependent β-oxidation in muscle, we aimed to test whether palmitoylation of eNOS is involved in palmitic acid (PA) regulation of left ventricular (LV) myocyte contraction from healthy (sham) and hypertensive (HTN) rats...
April 25, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28439258/diabetic-cardiomyopathy-an-immunometabolic-perspective
#19
REVIEW
Paras K Mishra, Wei Ying, Shyam Sundar Nandi, Gautam K Bandyopadhyay, Kaushik K Patel, Sushil K Mahata
The heart possesses a remarkable inherent capability to adapt itself to a wide array of genetic and extrinsic factors to maintain contractile function. Failure to sustain its compensatory responses results in cardiac dysfunction, leading to cardiomyopathy. Diabetic cardiomyopathy (DCM) is characterized by left ventricular hypertrophy and reduced diastolic function, with or without concurrent systolic dysfunction in the absence of hypertension and coronary artery disease. Changes in substrate metabolism, oxidative stress, endoplasmic reticulum stress, formation of extracellular matrix proteins, and advanced glycation end products constitute the early stage in DCM...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28437279/npy-impairs-cell-viability-and-mitochondrial-membrane-potential-through-ca2-and-p38-signaling-pathways-in-neonatal-rat-cardiomyocytes
#20
Jun Hu, Xuehua Xu, Yuanyi Zuo, Xiangting Gao, Yun Wang, Cunquan Xiong, Hongcheng Zhou, Shaohua Zhu
NPY is involved in stress cardiomyopathy (SCM). However, the associated mechanism for NPY-induced SCM remains unclear. In this study, we aimed to explore potential cell signaling pathways that are related to NPY-mediated cell viability in neonatal rat cardiomyocytes. We found that NPY induced cell viability suppression in cultured cardiomyocytes in a dose-dependent manner. After NPY treatment, the expression of CaN and p-CAMKII was increased significantly, and the phosphorylation of p38 but not ERK and JNK was detected...
April 18, 2017: Journal of Cardiovascular Pharmacology
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