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https://www.readbyqxmd.com/read/28521615/comprehensive-evaluation-of-usnic-acid-induced-cardiotoxicity-in-rats-by-sequential-cross-omics-analysis
#1
Y Yokouchi, M Imaoka, N Niino, N Kiyosawa, K Kai
Two-week administration of (+)-usnic acid (UA) induces mitochondrial swelling of cardiomyocytes, and toxicogenomic analysis of the heart revealed upregulation of oxidative stress, amino acid limitation, and endoplasmic reticulum stress-related genes in rats. To analyze the pathogenesis, UA was orally administrated to rats for 1, 4, 7, and 14 days, and sequential histopathological, genomic, and metabolomic analyses were performed on the heart, liver, and plasma. As a result, mitochondrial swelling of cardiomyocytes was observed on day 15 preceded by genomic upregulation on days 5 and 8...
January 1, 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28514771/istaroxime-a-potential-anticancer-drug-in-prostate-cancer-exerts-beneficial-functional-effects-in-healthy-and-diseased-human-myocardium
#2
Markus Wallner, Mounir Khafaga, Ewald Kolesnik, Aris Vafiadis, Gerold Schwantzer, Deborah M Eaton, Pero Curcic, Martin Köstenberger, Igor Knez, Peter P Rainer, Martin Pichler, Burkert Pieske, Dirk Von Lewinski
The current gold standard for prostate cancer treatment is androgen deprivation therapy and antiandrogenic agents. However, adverse cardiovascular events including heart failure can limit therapeutic use. Istaroxime, which combines Na+-K+-ATPase (NKA) inhibition with sarco/endoplasmic reticulum Ca2+-ATPase 2a (SERCA2a) stimulation, has recently shown promising anti-neoplastic effects in prostate cancer (PC) models and may also improve cardiac function. Considering the promising anticancer effects of istaroxime, we aimed to assess its functional effects on human myocardium...
April 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28513228/relationship-between-chop-gadd153-and-unstable-human-carotid-atherosclerotic-plaque
#3
Suping Wang, Meiyan Zhang, Zanhua Liu, Wuyang Yang, Junwei Shi, Victor Dean, Dong Chen
BACKGROUND AND AIMS: The signaling protein C/EBP homologous protein (CHOP) and corresponding growth-arrest-and-DNA-damage-inducible gene 153 (GADD153) is associated with endoplasmic reticulum stress (ERS), which can lead to apoptosis. Our study aims to elucidate the role of CHOP/GADD153 in unstable atherosclerotic (AS) plaque formation isolated from confounding factors such as diabetes mellitus, primary hyperlipidemia, autoimmune deficiencies/abnormalities, essential hypertension, chronic heart failure, chronic kidney disease, and smoking...
May 17, 2017: British Journal of Neurosurgery
https://www.readbyqxmd.com/read/28504910/fermented-moringa-oleifera-decreases-hepatic-adiposity-and-ameliorates-glucose-intolerance-in-high-fat-diet-induced-obese-mice
#4
Hyunchae Joung, Bobae Kim, Hyunjoon Park, Kyuyeon Lee, Hee-Hoon Kim, Ho-Cheol Sim, Hyun-Jin Do, Chang-Kee Hyun, Myoung-Sool Do
Metabolic diseases, such as glucose intolerance and nonalcoholic fatty-liver disease (NAFLD), are primary risk factors for life-threatening conditions such as diabetes, heart attack, stroke, and hepatic cancer. Extracts from the tropical tree Moringa oleifera show antidiabetic, antioxidant, anti-inflammatory, and anticancer effects. Fermentation can further improve the safety and nutritional value of certain foods. We investigated the efficacy of fermented M. oleifera extract (FM) against high-fat diet (HFD)-induced glucose intolerance and hepatic lipid accumulation and investigated the underlying mechanisms by analyzing expression of proteins and genes involved in glucose and lipid regulation...
May 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28500853/protective-effects-of-circulating-microvesicles-derived-from-myocardial-ischemic-rats-on-apoptosis-of-cardiomyocytes-in-myocardial-ischemia-reperfusion-injury
#5
Yao Wang, Su Wei, Yi-Lu Wang, Miao Liu, Man Shang, Qi Zhang, Yan-Na Wu, Ming-Lin Liu, Jun-Qiu Song, Yan-Xia Liu
OBJECTIVE: To investigate the effects of circulating microvesicles derived from myocardial ischemia (I-MVs) on apoptosis in myocardial ischemia/reperfusion (I/R) injury in rats. METHODS: I-MVs from rats undergoing myocardial left anterior descending (LAD) coronary artery ligation were isolated by ultracentrifugation from circulating blood and characterized by flow cytometry. I-MVs were administered intravenously (4.8 mg/kg) at 5 min before reperfusion procedure in I/R injury model which was induced by 30-min of ischemia and 120-min of reperfusion of LAD in rats...
April 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28498512/recurrent-atp2a2-p-pro602leu-mutation-differentiates-acrokeratosis-verruciformis-of-hopf-from-the-allelic-condition-darier-disease
#6
Anne Ronan, Angela Ingrey, Natalia Murray, Paul Chee
Darier disease and Acrokeratosis Verruciformis of Hopf (AKV) are rare disorders of keratinization with autosomal dominant inheritance and very distinct clinical pictures. Both have been shown to be caused by mutations in ATP2A2 (ATPase, Ca(++) transporting, cardiac muscle, slow-twitch) a gene encoding one of the SERCA (sarcoplasmic/endoplasmic reticulum calcium ATPase2) intracellular pumps with a crucial role in cell-to-cell adhesion in both skin and heart. While hundreds of different missense and nonsense mutations cause Darier disease, only one missense mutation, p...
May 12, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28497395/cardio-protective-effects-of-qishen-granule-on-sarcoplasmic-reticulum-ca-2-handling-in-heart-failure-rats
#7
Ling-Hui Lu, Chun Li, Qi-Yan Wang, Qian Zhang, Yi Zhang, Hui Meng, Yong Wang, Wei Wang
OBJECTIVES: To assess the effects of Qishen Granule (, QSG) on sarcoplasmic reticulum (SR) Ca(2+) handling in heart failure (HF) model of rats and to explore the underlying molecular mechanisms. METHODS: HF rat models were induced by left anterior descending coronary artery ligation surgery and high-fat diet feeding. Rats were randomly divided into sham (n=10), model (n=10), QSG (n=12, 2.2 g/kg daily) and metoprolol groups (n=12, 10.5 mg/kg daily). The therapeutic effects of QSG were evaluated by echocardiography and blood lipid testing...
May 11, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28495616/salvianolic-acid-b-attenuates-doxorubicin-induced-er-stress-by-inhibiting-trpc3-and-trpc6-mediated-ca-2-overload-in-rat-cardiomyocytes
#8
Rong-Chang Chen, Gui-Bo Sun, Jing-Xue Ye, Jian Wang, Miao-di Zhang, Xiao-Bo Sun
Doxorubicin (DOX)-induced cardiotoxicity is a clinically complex syndrome that leads to significant pain to cancer survivors. Endoplasmic reticulum (ER) stress has been suggested to be an important contributor to myocardium dysfunction during this phenomenon. Our previous study proved that Salvianolic acid B (Sal B) protected against doxorubicin induced cardiac dysfunction by inhibiting ER stress and cardiomyocyte apoptosis. However, the underlying molecular mechanism is not yet clearly. In this study, we investigated the protective effect and mechanisms of Sal B againest DOX-induced cardiac injury and ER stress in vivo and in vitro...
May 8, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28493471/what-role-does-the-stress-response-have-in-congestive-heart-failure
#9
REVIEW
Ahmed Badreddin, Youssef Fady, Hamdy Attia, Mohamed Hafez, Ahmed Khairallah, Dina Johar, Larry Bernstein
This review is concerned with cardiac malfunction as a result of an imbalance in protein proteostasis, the homeostatic balance between protein removal and regeneration in a long remodeling process involving the endoplasmic reticulum (ER) and the unfolded protein response (UPR). The importance of this is of special significance with regard to cardiac function as a high energy requiring muscular organ that has a high oxygen requirement and is highly dependent on mitochondria. The importance of mitochondria is not only concerned with high energy dependence on mitochondrial electron transport, but it also has a role in the signaling between the mitochondria and the ER under stress...
May 11, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28492915/sildenafil-treatment-in-heart-failure-with-preserved-ejection-fraction-targeted-metabolomic-profiling-in-the-relax-trial
#10
Hanghang Wang, Kevin Anstrom, Olga Ilkayeva, Michael J Muehlbauer, James R Bain, Steven McNulty, Christopher B Newgard, William E Kraus, Adrian Hernandez, G Michael Felker, Margaret Redfield, Svati H Shah
Importance: Phosphodiesterase-5 inhibition with sildenafil compared with a placebo had no effect on the exercise capacity or clinical status of patients with heart failure with preserved ejection fraction (HFpEF) in the PhosphodiesteRasE-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure with Preserved Ejection Fraction (RELAX) clinical trial. Metabolic impairments may explain the neutral results. Objective: To test the hypothesis that profiling metabolites in the RELAX trial would clarify the mechanisms of sildenafil effects and identify metabolites associated with clinical outcomes in HFpEF...
May 10, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/28487469/phosphoinositide-3-kinase-p110%C3%AE-gene-delivery-limits-diabetes-induced-cardiac-nadph-oxidase-and-cardiomyopathy-in-a-mouse-model-with-established-diastolic-dysfunction
#11
Darnel Prakoso, Miles J DeBlasio, Chengxue Qin, Sarah Rosli, Helen Kiriazis, Hongwei Qian, Xiao-Jun Du, Kate L Weeks, Paul Gregorevic, Julie R McMullen, Rebecca H Ritchie
Phosphoinositide 3-kinase [PI3K (p110α)] is able to negatively regulate the diabetes-induced increase in NADPH oxidase in the heart. Patients affected by diabetes exhibit significant cardiovascular morbidity and mortality, at least in part due to a cardiomyopathy characterised by oxidative stress and left ventricular (LV) dysfunction. Thus, PI3K (p110α) may represent a novel approach to protect the heart from diabetes-induced cardiac oxidative stress and dysfunction. In the current study, we investigated the therapeutic potential of a delayed intervention with cardiac-targeted PI3K gene therapy, administered to mice with established diabetes-induced LV diastolic dysfunction...
May 9, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28478799/role-of-microrna-124-in-cardiomyocyte-hypertrophy-inducedby-angiotensin-ii
#12
Q Bao, L Chen, J Li, M Zhao, S Wu, W Wu, X Liu
Cardiac hypertrophy is a crucial predictor of heart failure and is regulated by microRNAs. MicroRNA-124 (miR-124) is regarded as a prognostic indicator for outcomes after cardiac arrest. However, whether miR-124 participates in cardiac hypertrophy remains unclear. Therefore, our study aimed to determine the role of miR-124 in angiotensin II(AngII)-induced myocardial hypertrophy and the possible mechanism. Primary cultured rat neonatal cardiomyocytes(NCMs) were transfected with miR-124 mimics or inhibitor, followed by AngII stimulation...
April 29, 2017: Cellular and Molecular Biology
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/28472796/the-sodium-glucose-co-transporter-2-inhibitor-empagliflozin-protects-against-diabetic-cardiomyopathy-by-inhibition-of-the-endoplasmic-reticulum-stress-pathway
#14
Yang Zhou, Wei Wu
BACKGROUND/AIMS: This study aimed to determine whether or not the sodium-glucose co-transporter 2 inhibitor, empagliflozin (EMPA), can protect against diabetic cardiomyopathy (DCM) and to elucidate the related mechanism. METHODS: Rats were divided into the following four groups: a non-diabetic group; diabetic cardiomyopathy rats without EMPA treatment; and diabetic cardiomyopathy rats with EMPA treatment (low- and high-dose EMPA). Hemodynamic measurements were performed to evaluate left ventricular systolic and diastolic function...
May 4, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28439258/diabetic-cardiomyopathy-an-immunometabolic-perspective
#15
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/28426781/tauroursodeoxycholic-acid-tudca-attenuates-pressure-overload-induced-cardiac-remodeling-by-reducing-endoplasmic-reticulum-stress
#16
Shilpa Rani, Pradeep Kumar Sreenivasaiah, Jin Ock Kim, Mi Young Lee, Wan Seok Kang, Yong Sook Kim, Youngkeun Ahn, Woo Jin Park, Chunghee Cho, Do Han Kim
Pressure overload in the heart induces pathological hypertrophy and is associated with cardiac dysfunction. Apoptosis and fibrosis signaling initiated by the endoplasmic reticulum stress (ERS) is known to contribute to these maladaptive effects. The aim of this study was to investigate whether reduction of ERS by a known chemical chaperone, tauroursodeoxycholic acid (TUDCA) can attenuate pressure overload-induced cardiac remodeling in a mouse model of transverse aortic constriction (TAC). Oral administration of TUDCA at a dose of 300 mg/kg body weight (BW) in the TUDCA-TAC group reduced ERS markers (GRP78, p-PERK, and p-eIf2α), compared to the Vehicle (Veh)-TAC group...
2017: PloS One
https://www.readbyqxmd.com/read/28403128/an-oxygenated-and-transportable-machine-perfusion-system-fully-rescues-liver-grafts-exposed-to-lethal-ischemic-damage-in-a-pig-model-of-dcd-liver-transplantation
#17
Philippe Compagnon, Eric Levesque, Hassen Hentati, Mara Disabato, Julien Calderaro, Cyrille Feray, Anne Corlu, José Laurent Cohen, Ismail Ben Mosbah, Daniel Azoulay
BACKGROUND: Control of warm ischemia (WI) lesions that occur with donation after circulatory death (DCD) would significantly increase the donor pool for liver transplantation. We aimed to determine whether a novel, oxygenated and hypothermic machine perfusion device (HMP Airdrive system) improves the quality of livers derived from DCDs using a large animal model. METHODS: Cardiac arrest was induced in female large white pigs by IV injection of potassium chloride...
April 11, 2017: Transplantation
https://www.readbyqxmd.com/read/28402922/toxicity-of-triptolide-and-the-molecular-mechanisms-involved
#18
REVIEW
Chen Xi, Shaojun Peng, Zhengping Wu, Qingping Zhou, Jie Zhou
Triptolide (TP), a major active and toxic ingredient isolated from the traditional Chinese herb Tripterygium wilfordii Hook f. (TWHF). A widespread application of TP raises the question on the safety of its use in clinical settings. The metabolism of TP is mediated by hepatic cytochrome P450s, and a strong correlation exists between TP toxicity and CPY3A. Toxicity of TP and the molecular mechanisms of its toxic effects have been studied in recent years. Studies have demonstrated that TP exposure results in injury of various organs, including the liver, kidney, testes, ovary, and heart in animals and even in humans, according to clinical case reports...
June 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28395010/inflammation-and-metabolic-cardiomyopathy
#19
Kazuhiko Nishida, Kinya Otsu
Excessive feeding is associated with an increase in the incidence of chronic metabolic diseases, such as obesity, insulin resistance, and type 2 diabetes. Metabolic disturbance induces chronic low-grade inflammation in metabolically-important organs, such as the liver and adipose tissue. Many of the inflammatory signalling pathways are directly triggered by nutrients. The pro-inflammatory mediators in adipocytes and macrophages infiltrating adipose tissue promote both local and systemic pro-inflammatory status...
March 15, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28393439/effect-of-intracoronary-administration-of-aav1-serca2a-on-ventricular-remodelling-in-patients-with-advanced-systolic-heart-failure-results-from-the-agent-hf-randomized-phase-2-trial
#20
Jean-Sébastien Hulot, Joe-Elie Salem, Alban Redheuil, Jean-Philippe Collet, Shaida Varnous, Patrick Jourdain, Damien Logeart, Estelle Gandjbakhch, Claude Bernard, Stéphane N Hatem, Richard Isnard, Philippe Cluzel, Claude Le Feuvre, Pascal Leprince, Nadjib Hammoudi, François M Lemoine, David Klatzmann, Eric Vicaut, Michel Komajda, Gilles Montalescot, Anne-Marie Lompré, Roger J Hajjar
AIMS: Restoration of sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA2a) activity through gene transfer improved cardiac function in experimental and pilot studies in humans with heart failure. The AGENT-HF (NCT01966887) trial investigated the impact of adeno-associated virus (AAV1)/SERCA2a on ventricular remodelling using multimodality non-invasive cardiac imaging. METHODS AND RESULTS: AGENT-HF was a single centre, randomized, double-blind, placebo-controlled trial in adult patients with NYHA class III-IV ischaemic or non-ischaemic heart failure and left ventricular ejection fraction ≤35%...
April 10, 2017: European Journal of Heart Failure
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