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https://www.readbyqxmd.com/read/29152614/ataxia-telangiectasia-mutated-kinase-role-in-myocardial-remodeling
#1
Patsy Thrasher, Mahipal Singh, Krishna Singh
Ataxia-telangiectasia mutated kinase (ATM) is a serine/threonine kinase. Mutations in the ATM gene cause a rare autosomal multisystemic disease known as Ataxia-telangiectasia (AT). Individuals with mutations in both copies of the ATM gene suffer from increased susceptibility to ionizing radiation, predisposition to cancer, insulin resistance, immune deficiency, and premature aging. Patients with one mutated allele make-up ~1.4 to 2% of the general population. These individuals are spared from most of the symptoms of the disease...
2017: Journal of Rare Diseases Research & Treatment
https://www.readbyqxmd.com/read/29136764/cardiac-apoptosis-induced-under-high-glucose-condition-involves-activation-of-igf2r-signaling-in-h9c2-cardiomyoblasts-and-streptozotocin-induced-diabetic-rat-hearts
#2
Chih-Chung Feng, Sudhir Pandey, Ching-Yuang Lin, Chia-Yao Shen, Ruey-Lin Chang, Tung-Ti Chang, Ray-Jade Chen, Vijaya Padma Viswanadha, Yueh-Min Lin, Chih-Yang Huang
The insulin-like growth factor type 2 receptor (IGF2R) overexpression has been implicated in heart disease progression. Unregulated IGF2R signaling triggers cardiac hypertrophy, apoptosis, and cardiomyopathies. The present study investigated the role of IGF2R in cardiomyocyte apoptosis under high glucose (HG) levels and in streptozotocin (STZ) induced diabetic rat hearts. We found that IGF2 and IGF2R protein expression were highly upregulated under high glucose condition in H9c2 cells as well as in STZ induced diabetic rat hearts...
November 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29115461/histone-deacetylase-inhibition-of-cardiac-autophagy-in-rats-on-a-high%C3%A2-fat-diet-with-low%C3%A2-dose-streptozotocin-induced-type-2-diabetes-mellitus
#3
Ting-I Lee, Kuan-Jen Bai, Yao-Chang Chen, Ting-Wei Lee, Cheng-Chih Chung, Wen-Chih Tsai, Shin-Yi Tsao, Yu-Hsun Kao
Autophagy serves a role in preserving cellular homeostasis. Diabetes mellitus (DM) impairs cardiac autophagy and is associated with an accumulation of cytotoxic proteins that may provoke apoptosis and damage cardiomyocytes. Histone deacetylase (HDAC) inhibitors attenuate cardiac fibrosis and inflammation, and improve cardiomyopathy resulting from DM. However, the effect of HDAC inhibition on autophagy in DM cardiomyopathy has not been investigated. The purpose of the present study was to evaluate whether HDAC inhibition modulates cardiac autophagy and to investigate the potential mechanisms in type 2 DM (T2DM) hearts...
October 26, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29115400/global-gene-expression-analysis-combined-with-a-genomics-approach-for-the-identification-of-signal-transduction-networks-involved-in-postnatal-mouse-myocardial-proliferation-and-development
#4
Ruoxin Wang, Chao Su, Xinting Wang, Qiang Fu, Xingjie Gao, Chunyan Zhang, Jie Yang, Xi Yang, Minxin Wei
Mammalian cardiomyocytes may permanently lose their ability to proliferate after birth. Therefore, studying the proliferation and growth arrest of cardiomyocytes during the postnatal period may enhance the current understanding regarding this molecular mechanism. The present study identified the differentially expressed genes in hearts obtained from 24 h‑old mice, which contain proliferative cardiomyocytes; 7‑day‑old mice, in which the cardiomyocytes are undergoing a proliferative burst; and 10‑week‑old mice, which contain growth‑arrested cardiomyocytes, using global gene expression analysis...
November 3, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29109913/comparative-analysis-of-the-microrna-transcriptome-between-yak-and-cattle-provides-insight-into-high-altitude-adaptation
#5
Jiuqiang Guan, Keren Long, Jideng Ma, Jinwei Zhang, Dafang He, Long Jin, Qianzi Tang, Anan Jiang, Xun Wang, Yaodong Hu, Shilin Tian, Zhi Jiang, Mingzhou Li, Xiaolin Luo
Extensive and in-depth investigations of high-altitude adaptation have been carried out at the level of morphology, anatomy, physiology and genomics, but few investigations focused on the roles of microRNA (miRNA) in high-altitude adaptation. We examined the differences in the miRNA transcriptomes of two representative hypoxia-sensitive tissues (heart and lung) between yak and cattle, two closely related species that live in high and low altitudes, respectively. In this study, we identified a total of 808 mature miRNAs, which corresponded to 715 pre-miRNAs in the two species...
2017: PeerJ
https://www.readbyqxmd.com/read/29109032/molecular-mechanisms-of-cardiac-pathology-in-diabetes-experimental-insights
#6
REVIEW
U Varma, P Koutsifeli, V L Benson, K M Mellor, L M D Delbridge
Diabetic cardiomyopathy is a distinct pathology independent of co-morbidities such as coronary artery disease and hypertension. Diminished glucose uptake due to impaired insulin signaling and decreased expression of glucose transporters is associated with a shift towards increased reliance on fatty acid oxidation and reduced cardiac efficiency in diabetic hearts. The cardiac metabolic profile in diabetes is influenced by disturbances in circulating glucose, insulin and fatty acids, and alterations in cardiomyocyte signaling...
November 3, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29098797/acylated-ghrelin-treatment-normalizes-skeletal-muscle-mitochondrial-oxidative-capacity-and-akt-phosphorylation-in-rat-chronic-heart-failure
#7
Rocco Barazzoni, Gianluca Gortan Cappellari, Sandra Palus, Pierandrea Vinci, Giulia Ruozi, Michela Zanetti, Annamaria Semolic, Nicole Ebner, Stephan von Heahling, Gianfranco Sinagra, Mauro Giacca, Jochen Springer
BACKGROUND: Chronic heart failure (CHF) is associated with skeletal muscle abnormalities contributing to exercise intolerance, muscle loss, and negative impact on patient prognosis. A primary role has been proposed for mitochondrial dysfunction, which may be induced by systemic and tissue inflammation and further contribute to low insulin signalling. The acylated form of the gastric hormone ghrelin (AG) may improve mitochondrial oxidative capacity and insulin signalling in both healthy and diseased rodent models...
November 3, 2017: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/29098623/the-igf1-pi3k-akt-signaling-pathway-in-mediating-exercise-induced-cardiac-hypertrophy-and-protection
#8
Kate L Weeks, Bianca C Bernardo, Jenny Y Y Ooi, Natalie L Patterson, Julie R McMullen
Regular physical activity or exercise training can lead to heart enlargement known as cardiac hypertrophy. Cardiac hypertrophy is broadly defined as an increase in heart mass. In adults, cardiac hypertrophy is often considered a poor prognostic sign because it often progresses to heart failure. Heart enlargement in a setting of cardiac disease is referred to as pathological cardiac hypertrophy and is typically characterized by cell death and depressed cardiac function. By contrast, physiological cardiac hypertrophy, as occurs in response to chronic exercise training (i...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29079702/metallothionein-preserves-akt2-activity-and-cardiac-function-via-inhibiting-trb3-in-diabetic-hearts
#9
Junlian Gu, Xiaoqing Yan, Xiaozhen Dai, Yuehui Wang, Qian Lin, Jian Xiao, Shanshan Zhou, Jian Zhang, Kai Wang, Jun Zeng, Ying Xin, Michelle T Barati, Chi Zhang, Yang Bai, Yan Li, Paul N Epstein, Kupper A Wintergerst, Xiaokun Li, Yi Tan, Lu Cai
Cardiac insulin resistance is a key pathogenic factor for diabetic cardiomyopathy (DCM), but the mechanism remains largely unclear. We found that diabetic hearts exhibited decreased phosphorylation of total Akt and isoform Akt2 but not Akt1 in wild type (WT) male FVB mice, which was accompanied by attenuation of Akt downstream glucose metabolic signal; All these signal changes were not observed in metallothionein cardiac-specific transgenic (MT-TG) hearts. Furthermore, insulin-induced glucose metabolic signals were attenuated only in WT diabetic hearts...
October 27, 2017: Diabetes
https://www.readbyqxmd.com/read/29058194/characterization-of-mc4r-regulation-of-the-kir7-1-channel-using-the-tl-flux-assay
#10
Michael J Litt, Roger D Cone, Masoud Ghamari-Langroudi
The family of inward rectifying potassium channels (Kir channels) plays crucial roles in the regulation of heart rhythms, renal excretion, insulin release, and neuronal activity. Their dysfunction has been attributed to numerous diseases such as cardiac arrhythmia, kidney failure and electrolyte imbalance, diabetes mellitus, epilepsy, retinal degeneration, and other neuronal disorders. We have recently demonstrated that the melanocortin-4 receptor (MC4R), a Gαs-coupled GPCR, regulates Kir7.1 activity through a mechanism independent of Gαs and cAMP...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29052864/short-term-hypoxia-upregulated-mas-receptor-expression-to-repress-the-at1-r-signaling-pathway-and-attenuate-ang-ii-induced-cardiomyocyte-apoptosis
#11
Ruey-Lin Chang, Chih-Fen Chang, Da-Tong Ju, Tsung-Jung Ho, Tung-Ti Chang, Jing-Wei Lin, Jia-Chun Le, Shiu-Min Cheng, Cecilia-Hsuan Day, V Vijaya Padma, Chih-Yang Huang
Hypertension-stimulated cardiac hypertrophy and apoptosis play critical roles in the progression of heart failure. Our previous study suggested that hypertensive angiotensin II (Ang II) enhanced insulin-like growth factor receptor II (IGF-IIR) expression and cardiomyocyte apoptosis, which are involved JNK activation, sirtuin1 (SIRT1) degradation, and heat-shock transcription factor 1 (HSF1) acetylation. Moreover, previous studies have implied that short-term hypoxia (STH) might exert cardioprotective effects...
October 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29043508/the-role-of-pi3k%C3%AE-isoform-in-cardioprotection
#12
Xavier Rossello, Jaime A Riquelme, Zhenhe He, Stasa Taferner, Bart Vanhaesebroeck, Sean M Davidson, Derek M Yellon
Ischemic preconditioning (IPC) limits myocardial infarct size through the activation of the PI3K-Akt signal cascade; however, little is known about the roles of individual PI3K isoforms in cardioprotection. We aimed, therefore, to elucidate the role of the PI3Kα isoform in cardioprotection Pharmacological PI3Kα inhibition was assessed in isolated-perfused mouse hearts subjected to ischemia/reperfusion injury (IRI), either during the IPC procedure or at reperfusion. PI3Kα inhibition abrogated the IPC-induced protective effect at reperfusion, but not when given only during the IPC protocol...
October 17, 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/29021167/high-density-lipoprotein-delivered-after-myocardial-infarction-increases-cardiac-glucose-uptake-and-function-in-mice
#13
Sarah E Heywood, Adele L Richart, Darren C Henstridge, Karen Alt, Helen Kiriazis, Claire Zammit, Andrew L Carey, Helene L Kammoun, Lea M Delbridge, Medini Reddy, Yi-Ching Chen, Xiao-Jun Du, Christoph E Hagemeyer, Mark A Febbraio, Andrew L Siebel, Bronwyn A Kingwell
Protecting the heart after an acute coronary syndrome is a key therapeutic goal to support cardiac recovery and prevent progression to heart failure. A potential strategy is to target cardiac glucose metabolism at the early stages after ischemia when glycolysis is critical for myocyte survival. Building on our discovery that high-density lipoprotein (HDL) modulates skeletal muscle glucose metabolism, we now demonstrate that a single dose of reconstituted HDL (rHDL) delivered after myocardial ischemia increases cardiac glucose uptake, reduces infarct size, and improves cardiac remodeling in association with enhanced functional recovery in mice...
October 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28989026/activation-of-nuclear-%C3%AE-catenin-c-myc-axis-promotes-oxidative-stress-injury-in-streptozotocin-induced-diabetic-cardiomyopathy
#14
Peng Liu, Jianfang Su, Xixi Song, Shixiao Wang
Myocardial oxidative stress injury plays a crucial role in the pathogenesis of diabetic cardiomyopathy (DCM). Wnt/β-catenin signaling has been reported to involve in various heart diseases. However, the underlying mechanism associated with β-catenin in DCM remains elusive. This study intended to explore the effect of β-catenin on oxidative damage of DCM by establishing streptozotocin (STZ)-induced diabetic mouse model and hydrogen peroxide (H2O2)-treated myocardial cell model. Cardiac oxidative stress in DCM was detected by measurements of lipid peroxidation and anti-oxidative enzyme activities as well as DHE staining...
December 2, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28967097/chronic-treatment-with-novel-nanoformulated-micelles-of-rapamycin-rapatar-protects-diabetic-heart-against-ischemia-reperfusion-injury
#15
Arun Samidurai, Fadi N Salloum, David Durrant, Olga B Chernova, Rakesh C Kukreja, Anindita Das
BACKGROUND: Enhanced mammalian target of rapamycin (mTOR) signaling contributes to the pathogenesis of diabetes and plays a critical role in myocardial ischemia/reperfusion (I/R) injury. Rapatar is a novel nanoformulated micellar of rapamycin, a putative inhibitor of mTOR, that have been rationally designed to increase water solubility of rapamycin in order to facilitate oral administration and enhance bioavailability. We examined the effect of Rapatar in improving metabolic status and protection against myocardial I/R injury in type 2 diabetic (T2D) mice...
October 1, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28942514/intrauterine-hyperglycemia-induced-inflammatory-signalling-via-the-receptor-for-advanced-glycation-end-products-in-the-cardiac-muscle-of-the-infants-of-diabetic-mother-rats
#16
Ritsuko Kawaharada, Haruna Masuda, Zhenyi Chen, Eric Blough, Tomoko Kohama, Akio Nakamura
PURPOSE: Gestational diabetes is associated with increased risk to the health of the mother and her offspring. In particular, the infants of diabetic mothers (IDMs) exhibit elevated levels of preterm birth, macrosomia, hypoglycemia, hypocalcemia, and cardiomyopathy. We have previously reported that IDMs showed abnormalities in cardiac Akt-related insulin signalling, and that these deficiencies in Akt-related signalling were attenuated by supplementing the maternal diet with fish-oil. Herein, we investigated whether the eicosapentaenoic acid (EPA) found in fish oil can be used to attenuate diabetes associated impairments in cardiomyocyte signalling...
September 23, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28928113/pdk4-inhibits-cardiac-pyruvate-oxidation-in-late-pregnancy
#17
Laura X Liu, Glenn C Rowe, Steven Yang, Jian Li, Federico Damilano, Mun Chun Chan, Wenyun Lu, Cholsoon Jang, Shogo Wada, Michael Morley, Michael Hesse, Bernd K Fleischmann, Joshua Rabinowitz, Saumya Das, Anthony Rosenzweig, Zoltan Arany
Rationale: Pregnancy profoundly alters maternal physiology. The heart hypertrophies during pregnancy, but its metabolic adaptations are not well understood. Objective: To determine the mechanisms underlying cardiac substrate use during pregnancy. Methods and Results: We use here (13)C-glucose, (13)C-lactate, and (13)C-fatty acid tracing analyses to show that hearts in late pregnant mice increase fatty acid uptake and oxidation into the tricarboxylic acid (TCA) cycle, while reducing glucose and lactate oxidation...
September 19, 2017: Circulation Research
https://www.readbyqxmd.com/read/28917508/insulin-dependent-metabolic-and-inotropic-responses-in-the-heart-are-modulated-by-hydrogen-peroxide-from-nadph-oxidase-isoforms-nox2-and-nox4
#18
Benjamin Steinhorn, Juliano L Sartoretto, Andrea Sorrentino, Natalia Romero, Hermann Kalwa, E Dale Abel, Thomas Michel
RATIONALE: Hydrogen peroxide (H2O2) is a stable reactive oxygen species (ROS) that has long been implicated in insulin signal transduction in adipocytes. However, H2O2's role in mediating insulin's effects on the heart are unknown. OBJECTIVE: We investigated the role of H2O2 in activating insulin-dependent changes in cardiac myocyte metabolic and inotropic pathways. The sources of insulin-dependent H2O2 generation were also studied. METHODS AND RESULTS: In addition to the canonical role of insulin in modulating cardiac metabolic pathways, we found that insulin also inhibited beta adrenergic-induced increases in cardiac contractility...
September 14, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28915960/pleiotropic-effects-of-metformin-to-rescue-statin-induced-muscle-injury-and-insulin-resistance-a-proposed-mechanism-and-potential-clinical-implications
#19
Nicholas W Carris, Srinivas M Tipparaju, David J Magness, Kalyan C Chapalamadugu, Ronald R Magness
The 2013 American Heart Association Blood Cholesterol Guidelines increased the number of patients recommended for statin therapy in the United States to 56million. Two common statin side effects are muscle pain, referred to as "statin-associated muscle symptoms", and increased risk for new onset type-2-diabetes mellitus. Up to 25% of statin users report muscle symptoms resulting in many patients being switched to lower dose or lower potency statins, or refusing statins altogether. The most likely signaling mechanisms for statin-associated muscle symptoms overlaps with the proposed mechanism of statin-induced insulin resistance...
September 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28867579/socs2-exacerbates-myocardial-injury-induced-by-ischemia-reperfusion-in-diabetic-mice-and-h9c2-cells-through-inhibiting-the-jak-stat-igf-1-pathway
#20
Mengting Sheng, Zirui Huang, Liming Pan, Min Yu, Cai Yi, Lin Teng, Ling He, Chen Gu, Chunli Xu, Junming Li
AIMS: This study aimed to investigate potential candidates and molecular mechanisms of myocardial ischemia/reperfusion (I/R) injury (MIRI) in type 2 diabetes mellitus. MAIN METHODS: Type 2 diabetic and myocardial I/R mouse models were established with a high fat-diet (HFD) for 24weeks and subjecting to global ischemia/reperfusion for 1h/3h, respectively. Microarray analysis was applied to screen differentially expressed genes (DEGs) in the hearts of these mice. Moreover, H9c2 cells were treated with high glucose (HG) and/or hypoxia and reoxygenation (H/R)...
November 1, 2017: Life Sciences
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