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https://www.readbyqxmd.com/read/28431892/a-humanized-hla-dr4-mouse-model-for-autoimmune-myocarditis
#1
M Emrah Şelli, Anita C Thomas, David C Wraith, Andrew C Newby
Myocarditis, the principal cause of dilated cardiomyopathy and heart failure in young adults, is associated with autoimmunity to human cardiac α-myosin (hCAM) and the DR4 allele of human major histocompatibility II (MHCII). We developed an hCAM-induced myocarditis model in human HLA-DR4 transgenic mice that lack all mouse MHCII genes, demonstrating that immunization for 3weeks significantly increased splenic T-cell proliferative responses and titres of IgG1 and IgG2c antibodies, abolished weight gain, provoked cardiac inflammation and significantly impaired cardiac output and fractional shortening, by echocardiography, compared to adjuvant-injected mice...
April 18, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28423592/protective-effect-of-hydrogen-sulphide-against-myocardial-hypertrophy-in-mice
#2
Mingjing Shao, Chuanjun Zhuo, Ronghuan Jiang, Guangdong Chen, Jianmin Shan, Jing Ping, Hongjun Tian, Lina Wang, Chongguang Lin, Lirong Hu
Cardiac hypertrophy is a critical component of phenotype in the failing heart. Recently, increasing evidence has demonstrated that oxidative stress plays an important role in the pathogenesis of myocardial hypertrophy. In the present study, we generated a mouse model of transverse aortic constriction (TAC) to investigate whether hydrogen sulfide (H2S) has protective effects against cardiac hypertrophy. Left ventricular structure was analyzed by two-dimensional echocardiography. Oxidative stress was evaluated by measuring malondialdehyde, superoxide dismutase, glutathione peroxidase and reactive oxygen specie in the myocardium...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410273/up-regulation-of-intracellular-calcium-handling-underlies-the-recovery-of-endotoxemic-cardiomyopathy-in-mice
#3
Justin C Morse, Joanne Huang, Natasha Khona, Edward J Miller, Deborah A Siwik, Wilson S Colucci, Ion A Hobai
BACKGROUND: In surviving patients, sepsis-induced cardiomyopathy is spontaneously reversible. In the absence of any experimental data, it is generally thought that cardiac recovery in sepsis simply follows the remission of systemic inflammation. Here the authors aimed to identify the myocardial mechanisms underlying cardiac recovery in endotoxemic mice. METHODS: Male C57BL/6 mice were challenged with lipopolysaccharide (7 μg/g, intraperitoneally) and followed for 12 days...
April 14, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28405943/myocardial-oxidative-stress-correlates-with-left-ventricular-dysfunction-on-strain-echocardiography-in-a-rodent-model-of-sepsis
#4
Bereketeab Haileselassie, Erik Su, Iraklis Pozios, Diego F Niño, Hongyun Liu, Dai-Yin Lu, Ioannis Ventoulis, William B Fulton, Chhinder P Sodhi, David Hackam, Brian O'Rourke, Theodore Abraham
BACKGROUND: Recognition of cardiomyopathy in sepsis can be challenging due to the limitations of conventional measures such as ejection fraction (EF) and fractional shortening (FS) in the context of variable preload and afterload conditions. This study correlates myocardial function using strain echocardiography (SE) with cardiomyocyte oxidative stress in a murine model of sepsis. METHODS: C57BL/6J mice were randomized into control (n = 10), sham (n = 25), and a cecal ligation and puncture (CLP) (n = 33) model of sepsis...
December 2017: Intensive Care Medicine Experimental
https://www.readbyqxmd.com/read/28395979/interest-of-colchicine-in-the-treatment-of-acute-myocardial-infarct-responsible-for-heart-failure-in-a-mouse-model
#5
Mariama Akodad, Jérémy Fauconnier, Pierre Sicard, Fabien Huet, Florence Blandel, Annick Bourret, Pascal de Santa Barbara, Sylvain Aguilhon, Marion LeGall, Gérald Hugon, Alain Lacampagne, François Roubille
BACKGROUND: Inflammation is deeply involved in the pathophysiology of ischemia-reperfusion (I/R) lesions and ventricular remodeling due to an acute myocardial infarction (AMI). Colchicine as a pleiotropic anti-inflammatory molecule may exert cardioprotective effects under acute ischemia. Here, we aimed to evaluate the impact of colchicine on reperfusion injury in a mouse model. METHOD: Myocardial ischemia/reperfusion (I/R) injury was induced in C57BL/6 male mice, after 45min ligation of the left coronary artery followed by reperfusion...
April 1, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28394363/interleukin-18-mediates-cardiac-dysfunction-induced-by-western-diet-independent-of-obesity-and-hyperglycemia-in-the-mouse
#6
S Carbone, P J H Lee, A G Mauro, E Mezzaroma, R Buzzetti, B Van Tassell, A Abbate, S Toldo
Obesity and diabetes are independent risk factors for heart failure and are associated with the consumption of diet rich in saturated fat and sugar, Western diet (WD), known to induce cardiac dysfunction in the mouse through incompletely characterized inflammatory mechanisms. We hypothesized that the detrimental cardiac effects of WD are mediated by interleukin-18 (IL-18), pro-inflammatory cytokine linked to cardiac dysfunction. C57BL/6J wild-type male mice and IL-18 knockout male mice were fed high-saturated fat and high-sugar diet for 8 weeks...
April 10, 2017: Nutrition & Diabetes
https://www.readbyqxmd.com/read/28393127/novel-junctophilin-2-mutation-a405s-is-associated-with-basal-septal-hypertrophy-and-diastolic-dysfunction
#7
Ann P Quick, Andrew P Landstrom, Qiongling Wang, David L Beavers, Julia O Reynolds, Giselle Barreto-Torres, Viet Tran, Jordan Showell, Leonne E Philippen, Shaine A Morris, Darlene Skapura, J Martijn Bos, Steen E Pedersen, Robia G Pautler, Michael J Ackerman, Xander H T Wehrens
BACKGROUND: Hypertrophic cardiomyopathy (HCM), defined as asymmetric left ventricular hypertrophy, is a leading cause of cardiac death in the young. Perturbations in calcium (Ca(2+)) handling proteins have been implicated in the pathogenesis of HCM. JPH2-encoded junctophilin 2 is a major component of the junctional membrane complex, the subcellular microdomain involved in excitation-contraction coupling. We hypothesized that a novel JPH2 mutation identified in patients with HCM is causally linked to HCM, and alters intracellular Ca(2+) signaling in a pro-hypertrophic manner...
February 2017: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/28377725/gut-microbiota-dependent-metabolite-trimethylamine-n-oxide-contributes-to-cardiac-dysfunction-in-western-diet-induced-obese-mice
#8
Kui Chen, Xiaoqian Zheng, Mingchen Feng, Dongliang Li, Hongqi Zhang
Excessive consumption of diets high in sugars and saturated fat, frequently known as western diet (WD), may lead to obesity and metabolic syndrome. Recent evidence shows that WD-induced obesity impairs cardiac function, but the underlying mechanisms are not fully understood. Trimethylamine N-oxide (TMAO), a gut microbiota-dependent metabolite of specific dietary nutrients, has emerged as a key contributor to cardiovascular disease pathogenesis. We tested the hypothesis that elevated circulating TMAO levels contribute to cardiac dysfunction in WD-induced obesity...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28371863/hypercontractile-mutant-of-ventricular-myosin-essential-light-chain-leads-to-disruption-of-sarcomeric-structure-and-function-and-results-in-restrictive-cardiomyopathy-in-mice
#9
Chen-Ching Yuan, Katarzyna Kazmierczak, Jingsheng Liang, Rosemeire Kanashiro-Takeuchi, Thomas C Irving, Aldrin V Gomes, Yihua Wang, Thomas P Burghardt, Danuta Szczesna-Cordary
Aims: The E143K (Glu→Lys) mutation in the myosin essential light chain (ELC) has been associated with restrictive cardiomyopathy (RCM) in humans, but the mechanisms that underlie the development of defective cardiac function are unknown. Using transgenic E143K-RCM mice, we sought to determine the molecular and cellular triggers of E143K-induced heart remodeling. Methods and Results: The E143K-induced abnormalities in cardiac function and morphology observed by echocardiography and invasive hemodynamics were paralleled by augmented active and passive tension measured in skinned papillary muscle fibers compared with wild-type (WT)-generated force...
March 23, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28368517/enhanced-glycolytic-metabolism-contributes-to-cardiac-dysfunction-in-polymicrobial-sepsis
#10
Zhibo Zheng, He Ma, Xia Zhang, Fei Tu, Xiaohui Wang, Tuanzhu Ha, Min Fan, Li Liu, Jingjing Xu, Kaiking Yu, Ruitao Wang, John Kalbfleisch, Race Kao, David Williams, Chuanfu Li
Background: Cardiac dysfunction is present in >40% of sepsis patients and is associated with mortality rates of up to 70%. Recent evidence suggests that glycolytic metabolism plays a critical role in host defense and inflammation. Activation of Toll-like receptors on immune cells can enhance glycolytic metabolism. This study investigated whether modulation of glycolysis by inhibition of hexokinase will be beneficial to septic cardiomyopathy. Methods: Male C57B6/J mice were treated with a hexokinase inhibitor (2-deoxy-D-glucose, 2-DG, 0...
March 22, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28366472/mice-or-nice-an-economic-evaluation-of-clinical-decision-rules-in-the-diagnosis-of-heart-failure-in-primary-care
#11
Mark Monahan, Pelham Barton, Clare J Taylor, Andrea K Roalfe, F D Richard Hobbs, Martin Cowie, Russell Davis, Jon Deeks, Jonathan Mant, Deborah McCahon, Theresa McDonagh, George Sutton, Lynda Tait
BACKGROUND: Detection and treatment of heart failure (HF) can improve quality of life and reduce premature mortality. However, symptoms such as breathlessness are common in primary care, have a variety of causes and not all patients require cardiac imaging. In systems where healthcare resources are limited, ensuring those patients who are likely to have HF undergo appropriate and timely investigation is vital. DESIGN: A decision tree was developed to assess the cost-effectiveness of using the MICE (Male, Infarction, Crepitations, Edema) decision rule compared to other diagnostic strategies to identify HF patients presenting to primary care...
March 2, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28362400/minimally-invasive-transverse-aortic-constriction-in-mice
#12
Aung Moe Zaw, Connor M Williams, Helen K W Law, Billy Kwok Chong Chow
Minimally invasive transverse aortic constriction (MTAC) is a more desirable method for the constriction of the transverse aorta in mice than standard open-chest transverse aortic constriction (TAC). Although transverse aortic constriction is a highly functional method for the induction of high pressure in the left ventricle, it is a more difficult and lengthy procedure due to its use of artificial ventilation with tracheal intubation. TAC is oftentimes also less survivable, as the newer method, MTAC, neither requires the cutting of the ribs and intercostal muscles nor tracheal intubation with a ventilation setup...
March 14, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28351964/left-ventricular-remodeling-leads-to-heart-failure-in-mice-with-cardiac-specific-overexpression-of-vegf-b167-echocardiography-and-magnetic-resonance-imaging-study
#13
Line Lottonen-Raikaslehto, Riina Rissanen, Erika Gurzeler, Mari Merentie, Jenni Huusko, Jurgen E Schneider, Timo Liimatainen, Seppo Ylä-Herttuala
Cardiac-specific overexpression of vascular endothelial growth factor (VEGF)-B167 is known to induce left ventricular hypertrophy due to altered lipid metabolism, in which ceramides accumulate to the heart and cause mitochondrial damage. The aim of this study was to evaluate and compare different imaging methods to find the most sensitive way to diagnose at early stage the progressive left ventricular remodeling leading to heart failure. Echocardiography and cardiovascular magnetic resonance imaging were compared for imaging the hearts of transgenic mice with cardiac-specific overexpression of VEGF-B167 and wild-type mice from 5 to 14 months of age at several time points...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28350070/tieg1-deficiency-confers-enhanced-myocardial-protection-in-the-infarcted-heart-by-mediating-the-pten-akt-signalling-pathway
#14
Mingqiu Cen, Pengfei Hu, Zhaobin Cai, Tianfu Fang, Jiancheng Zhang, Ming Lu
The transforming growth factor (TGF)-β-inducible early gene-1 (TIEG1) plays a crucial role in modulating cell apoptosis and proliferation in a number of diseases, including pancreatic cancer, leukaemia and osteoporosis. However, the functional role of TIEG1 in the heart has not been fully defined. In this study, we first investigated the role of TIEG1 in ischaemic heart disease. For in vitro experiments, cardiomyocytes were isolated from both TIEG1 knockout (KO) and wile-type (WT) mice, and the apoptotic ratios were evaluated after a 48‑h ischaemic insult...
February 13, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28349937/biodegradable-polymeric-nanocapsules-prevent-cardiotoxicity-of-anti-trypanosomal-lychnopholide
#15
Renata Tupinambá Branquinho, Jérôme Roy, Charlotte Farah, Giani Martins Garcia, Franck Aimond, Jean-Yves Le Guennec, Dênia Antunes Saude-Guimarães, Andrea Grabe-Guimaraes, Vanessa Carla Furtado Mosqueira, Marta de Lana, Sylvain Richard
Chagas disease is a neglected parasitic disease caused by the protozoan Trypanosoma cruzi. New antitrypanosomal options are desirable to prevent complications, including a high rate of cardiomyopathy. Recently, a natural substance, lychnopholide, has shown therapeutic potential, especially when encapsulated in biodegradable polymeric nanocapsules. However, little is known regarding possible adverse effects of lychnopholide. Here we show that repeated-dose intravenous administration of free lychnopholide (2...
March 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28347539/a-novel-murine-model-of-marfan-syndrome-accelerates-aortopathy-and-cardiomyopathy
#16
Nicholas B Cavanaugh, Lan Qian, Nicole M Westergaard, William J Kutschke, Ella J Born, Joseph W Turek
BACKGROUND: Marfan syndrome (MFS) represents a genetic disorder with variable phenotypic expression. The main cardiovascular sequelae of MFS include aortic aneurysm/dissection and cardiomyopathy. Although significant advances in the understanding of transforming growth factor beta signaling have led to promising therapeutic targets for the treatment of aortopathy, clinical studies have tempered this optimism. In particular, these studies suggest additional signaling pathways that play a significant role in disease progression...
March 24, 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28339476/transgenic-mice-overexpressing-desmocollin-2-dsc2-develop-cardiomyopathy-associated-with-myocardial-inflammation-and-fibrotic-remodeling
#17
Andreas Brodehl, Darrell D Belke, Lauren Garnett, Kristina Martens, Nelly Abdelfatah, Marcela Rodriguez, Catherine Diao, Yong-Xiang Chen, Paul M K Gordon, Anders Nygren, Brenda Gerull
BACKGROUND: Arrhythmogenic cardiomyopathy is an inherited heart muscle disorder leading to ventricular arrhythmias and heart failure, mainly as a result of mutations in cardiac desmosomal genes. Desmosomes are cell-cell junctions mediating adhesion of cardiomyocytes; however, the molecular and cellular mechanisms underlying the disease remain widely unknown. Desmocollin-2 is a desmosomal cadherin serving as an anchor molecule required to reconstitute homeostatic intercellular adhesion with desmoglein-2...
2017: PloS One
https://www.readbyqxmd.com/read/28319168/targeting-chronic-cardiac-remodeling-with-cardiac-progenitor-cells-in-a-murine-model-of-ischemia-reperfusion-injury
#18
Janine C Deddens, Dries A Feyen, Peter-Paul Zwetsloot, Maike A Brans, Sailay Siddiqi, Linda W van Laake, Pieter A Doevendans, Joost P Sluijter
BACKGROUND: Translational failure for cardiovascular disease is a substantial problem involving both high research costs and an ongoing lack of novel treatment modalities. Despite the progress already made, cell therapy for chronic heart failure in the clinical setting is still hampered by poor translation. We used a murine model of chronic ischemia/reperfusion injury to examine the effect of minimally invasive application of cardiac progenitor cells (CPC) in cardiac remodeling and to improve clinical translation...
2017: PloS One
https://www.readbyqxmd.com/read/28302646/eosinophil-derived-il-4-drives-progression-of-myocarditis-to-inflammatory-dilated-cardiomyopathy
#19
Nicola L Diny, G Christian Baldeviano, Monica V Talor, Jobert G Barin, SuFey Ong, Djahida Bedja, Allison G Hays, Nisha A Gilotra, Isabelle Coppens, Noel R Rose, Daniela Čiháková
Inflammatory dilated cardiomyopathy (DCMi) is a major cause of heart failure in children and young adults. DCMi develops in up to 30% of myocarditis patients, but the mechanisms involved in disease progression are poorly understood. Patients with eosinophilia frequently develop cardiomyopathies. In this study, we used the experimental autoimmune myocarditis (EAM) model to determine the role of eosinophils in myocarditis and DCMi. Eosinophils were dispensable for myocarditis induction but were required for progression to DCMi...
April 3, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28297585/electromechanical-conditioning-of-adult-progenitor-cells-improves-recovery-of-cardiac-function-after-myocardial-infarction
#20
Aida Llucià-Valldeperas, Carolina Soler-Botija, Carolina Gálvez-Montón, Santiago Roura, Cristina Prat-Vidal, Isaac Perea-Gil, Benjamin Sanchez, Ramon Bragos, Gordana Vunjak-Novakovic, Antoni Bayes-Genis
Cardiac cells are subjected to mechanical and electrical forces, which regulate gene expression and cellular function. Therefore, in vitro electromechanical stimuli could benefit further integration of therapeutic cells into the myocardium. Our goals were (a) to study the viability of a tissue-engineered construct with cardiac adipose tissue-derived progenitor cells (cardiac ATDPCs) and (b) to examine the effect of electromechanically stimulated cardiac ATDPCs within a myocardial infarction (MI) model in mice for the first time...
March 2017: Stem Cells Translational Medicine
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