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SERCA2a

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https://www.readbyqxmd.com/read/29288034/structural-and-functional-remodelling-of-the-atrioventricular-node-with-ageing-in-rats-the-role-of-hyperpolarization-activated-cyclic-nucleotide-gated-and-ryanodine-2-channels
#1
Yawer Saeed, Ian Temple, Zoltan Borbas, Andrew Atkinson, Joseph Yanni, Michal Maczewski, Urszula Mackiewicz, Mariam Aly, Sunil J R J Logantha, Clifford Garratt, Halina Dobrzynski
BACKGROUND: Ageing is associated with an increased incidence of atrioventricular nodal (AVN) dysfunction. OBJECTIVES: The aim of the study is to identify the structural and functional remodelling in the atrioventricular junction (AVJ) with ageing. METHODS: Electrophysiological, histology and immunohistochemistry experiments on male Wistar-Hanover rats aged 3months (n=24) and 2years (n=15) were performed. AH interval, Wenkebach cycle length (WBCL) and AVN effective refractory period (AVNERP) were measured...
December 26, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/29273502/mir-25-tough-decoy-enhances-cardiac-function-in-heart-failure
#2
Dongtak Jeong, Jimeen Yoo, Philyoung Lee, Sacha V Kepreotis, Ahyoung Lee, Christine Wahlquist, Brian D Brown, Changwon Kho, Mark Mercola, Roger J Hajjar
MicroRNAs are promising therapeutic targets, because their inhibition has the potential to normalize gene expression in diseased states. Recently, our group found that miR-25 is a key SERCA2a regulating microRNA, and we showed that multiple injections of antagomirs against miR-25 enhance cardiac contractility and function through SERCA2a restoration in a murine heart failure model. However, for clinical application, a more stable suppressor of miR-25 would be desirable. Tough Decoy (TuD) inhibitors are emerging as a highly effective method for microRNA inhibition due to their resistance to endonucleolytic degradation, high miRNA binding affinity, and efficient delivery...
November 26, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29249393/therapeutic-benefit-and-gene-network-regulation-by-combined-gene-transfer-of-apelin-fgf2-and-serca2a-into-ischemic-heart
#3
Edith Renaud-Gabardos, Florence Tatin, Fransky Hantelys, Benoît Lebas, Denis Calise, Oksana Kunduzova, Bernard Masri, Françoise Pujol, Pierre Sicard, Philippe Valet, Jérôme Roncalli, Xavier Chaufour, Barbara Garmy-Susini, Angelo Parini, Anne-Catherine Prats
Despite considerable advances in cardiovascular disease treatment, heart failure remains a public health challenge. In this context, gene therapy appears as an attractive approach, but clinical trials using single therapeutic molecules result in moderate benefit. With the objective of improving ischemic heart failure therapy, we designed a combined treatment, aimed to simultaneously stimulate angiogenesis, prevent cardiac remodeling, and restore contractile function. We have previously validated IRES-based vectors as powerful tools to co-express genes of interest...
November 16, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29229678/epitope-mapping-of-serca2a-identifies-an-antigenic-determinant-that-induces-mainly-atrial-myocarditis-in-a-j-mice
#4
Bharathi Krishnan, Chandirasegaran Massilamany, Rakesh H Basavalingappa, Arunakumar Gangaplara, Rajkumar A Rajasekaran, Muhammad Z Afzal, Vahid Khalilzad-Sharghi, You Zhou, Jean-Jack Riethoven, Shyam S Nandi, Paras K Mishra, Raymond A Sobel, Jennifer L Strande, David Steffen, Jay Reddy
Sarcoplasmic/endoplasmic reticulum Ca2+ adenosine triphosphatase (SERCA)2a, a critical regulator of calcium homeostasis, is known to be decreased in heart failure. Patients with myocarditis or dilated cardiomyopathy develop autoantibodies to SERCA2a suggesting that they may have pathogenetic significance. In this report, we describe epitope mapping analysis of SERCA2a in A/J mice that leads us to make five observations: 1) SERCA2a contains multiple T cell epitopes that induce varying degrees of myocarditis...
December 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29208771/advanced-iron-overload-cardiomyopathy-in-a-genetic-murine-model-is-rescued-by-resveratrol-therapy
#5
Subhash K Das, Pavel Zhabyeyev, Ratnadeep Basu, Vaibhav B Patel, Jason R B Dyck, Zamaneh Kassiri, Gavin Y Oudit
Iron-overload cardiomyopathy is prevalent on a worldwide basis and is a major co-morbidity in patients with genetic hemochromatosis and secondary iron overload. Therapies are limited in part due to lack of a valid pre-clinical model, which recapitulates advanced iron-overload cardiomyopathy. Male hemojuvelin knockout (HJVKO) mice, which lack hemojuvelin (HJV), a bone morphogenetic co-receptor protein required for hepcidin expression and systemic iron homeostasis, were fed a high iron diet starting at 4 weeks of age for a duration of 1 year...
December 5, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29191788/progressive-impairment-of-atrial-myocyte-function-during-left-ventricular-hypertrophy-and-heart-failure
#6
Florentina Pluteanu, Yulia Nikonova, Anna Holzapfel, Birgit Herzog, Anna Scherer, Judit Preisenberger, Jelena Plačkić, Katharina Scheer, Teodora Ivanova, Alicja Bukowska, Andreas Goette, Jens Kockskämper
Hypertensive heart disease (HHD) can cause left ventricular (LV) hypertrophy and heart failure (HF). It is unclear, though, which factors may contribute to the transition from compensated LV hypertrophy to HF in HHD. We hypothesized that maladaptive atrial remodeling with impaired atrial myocyte function would occur in advanced HHD and may be associated with the emergence of HF. Experiments were performed on atrial myocytes and tissue from old (15-25months) normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) with advanced HHD...
November 27, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29179218/puerarin-enhances-ca2-reuptake-and-ca2-content-of-sarcoplasmic-reticulum-in-murine-embryonic-stem-cell-derived-cardiomyocytes-via-upregulation-of-serca2a
#7
Lu Wang, Yurong Cui, Qinghua Liu, Yuanlong Song, Qinghua Hu, Ming Tang, Jürgen Hescheler, Jiaoya Xi
BACKGROUND/AIMS: The embryonic stem cell-derived cardiomyocytes (ES-CMs) serve as potential sources for cardiac regenerative therapy. However, the immature sarcoplasmic reticulum (SR) function of ES-CMs prevents its application. In this report, we examined the effect of puerarin, an isoflavone compound, on SR function of murine ES-CMs. METHODS: Murine ES-CMs were harvested by embryoid body-based differentiation method. Confocal calcium imaging and whole-cell patch clamps were performed to assess the function of SR...
November 28, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29174818/inhibition-of-advanced-glycation-endproduct-age-rescues-against-streptozotocin-induced-diabetic-cardiomyopathy-role-of-autophagy-and-er-stress
#8
Zhaohui Pei, Qinqin Deng, Sara A Babcock, Emily Y He, Jun Ren, Yingmei Zhang
Diabetes mellitus leads to oxidative stress and contractile dysfunction in the heart. Although several rationales have been speculated, the precise mechanism behind diabetic cardiomyopathy remains elusive. This study was designed to assess the role of inhibition of advanced glycation endproducts (AGE) in streptozotocin (STZ)-induced diabetic cardiac dysfunction. Cardiac contractile function was assessed in normal C57BL/6 and STZ (200mg/kg, single injection and maintained for 2 wks)-induced diabetic mice treated with or without the AGE inhibitor aminoguanidine (50mg/kg/d in drinking water) for 2 weeks using echocardiography and IonOptix MyoCam techniques...
November 22, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29169992/hax-1-regulates-serca2a-oxidation-and-degradation
#9
Philip A Bidwell, Guan-Sheng Liu, Narayani Nagarajan, Chi Keung Lam, Kobra Haghighi, George Gardner, Wen-Feng Cai, Wen Zhao, Luke Mugge, Elizabeth Vafiadaki, Despina Sanoudou, Jack Rubinstein, Djamel Lebeche, Roger Hajjar, Junichi Sadoshima, Evangelia G Kranias
Ischemia/reperfusion injury is associated with contractile dysfunction and increased cardiomyocyte death. Overexpression of the hematopoietic lineage substrate-1-associated protein X-1 (HAX-1) has been shown to protect from cellular injury but the function of endogenous HAX-1 remains obscure due to early lethality of the knockout mouse. Herein we generated a cardiac-specific and inducible HAX-1 deficient model, which uncovered an unexpected role of HAX-1 in regulation of sarco/endoplasmic reticulum Ca-ATPase (SERCA2a) in ischemia/reperfusion injury...
November 21, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29167149/three-dimensional-imaging-reveals-endo-sarco-plasmic-reticulum-containing-invaginations-within-the-muscle-nucleoplasm
#10
Shin-Haw Lee, Sina Hadipour-Lakmehsari, Tetsuaki Miyake, Anthony O Gramolini
The mammalian nucleus has invaginations from the cytoplasm, termed nucleoplasmic reticulum (NR). With increased resolution of cellular imaging, progress has been made in understanding the formation and function of NR. In fact, nucleoplasmic Ca2+ homeostasis has been implicated in the regulation of gene expression, DNA repair, and cell death. However, the majority of studies focus on cross-sectional or single plane analyses of NR invaginations, providing an incomplete assessment of its distribution and content...
November 22, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29150445/the-antiapoptotic-protein-hax-1-mediates-half-of-phospholamban-s-inhibitory-activity-on-calcium-cycling-and-contractility-in-the-heart
#11
Philip A Bidwell, Kobra Haghighi, Evangelia G Kranias
The antiapoptotic protein HS-associated protein X-1 (HAX-1) localizes to sarcoplasmic reticulum (SR) in the heart and interacts with the small membrane protein phospholamban (PLN), inhibiting the cardiac sarco/endoplasmic reticulum calcium ATPase (SERCA2a) in the regulation of overall calcium handling and heart muscle contractility. However, because global HAX-1 deletion causes early lethality, how much endogenous HAX-1 contributes to PLN's inhibitory activity on calcium cycling is unknown. We therefore generated a cardiac-specific and inducible knockout mouse model...
November 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29141547/cardioprotective-effects-of-serca2a-overexpression-against-ischemia-reperfusion-induced-injuries-in-rats
#12
Yan Jian, Li-Li Tian, Lin-Hui Wang, Xiao-Dong Zhao, Jing-Wei Chen, Koji Murao, Wei Zhu, Liang Dong, Guo-Qing Wang, Wan-Ping Sun, Guo-Xing Zhang
AIMS: The aim of the present study is to assess how genetically increased Sarcoplasmic reticulum Ca2+-ATPase (Serca2a) expression affects cardiac injury after ischemia/reperfusion (I/R) exposure and the related mechanisms involved. METHODS AND RESULTS: Rats were subjected to left anterior descending coronary artery (LAD) occlusion for 30 min followed by a 24-hour reperfusion. Cardiac function analysis revealed that cardiac function dramatically improved in Serca2a transgenic rats (Serca2aTG) rats compared to wild type (WT) rats...
November 10, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/29125993/substrate-and-mechanotransduction-influence-serca2a-localization-in-human-pluripotent-stem-cell-derived-cardiomyocytes-affecting-functional-performance
#13
Sebastian Martewicz, Elena Serena, Susi Zatti, Gordon Keller, Nicola Elvassore
Physical cues are major determinants of cellular phenotype and evoke physiological and pathological responses on cell structure and function. Cellular models aim to recapitulate basic functional features of their in vivo counterparts or tissues in order to be of use in in vitro disease modeling or drug screening and testing. Understanding how culture systems affect in vitro development of human pluripotent stem cell (hPSC)-derivatives allows optimization of cellular human models and gives insight in the processes involved in their structural organization and function...
October 16, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29073670/differential-effect-of-articaine-on-sarcoendoplasmic-reticulum-calcium-adenosine-triphosphatase-of-medial-pterygoid-muscle
#14
Carolina de la Cal, Gabriel Germán Trinks, Santiago Corti, Gabriel Antonio Sánchez
AIMS: To determine the effect of articaine on sarcoendoplasmic reticulum calcium adenosine triphosphatase (SERCA) isoforms of the medial pterygoid muscle. METHODS: Native SERCA from the medial pterygoid muscles of 24 rabbits was isolated by ultracentrifugation, and its isoforms were purified by chromatography and assessed by enzyme-linked immunosorbent assay (ELISA). SERCA activity and calcium transport capability were determined by using colorimetric and radioisotopic methods...
October 2017: Journal of Oral & Facial Pain and Headache
https://www.readbyqxmd.com/read/29029787/early-testosterone-replacement-attenuates-intracellular-calcium-dyshomeostasis-in-the-heart-of-testosterone-deprived-male-rats
#15
Punate Weerateerangkul, Krekwit Shinlapawittayatorn, Siripong Palee, Nattayaporn Apaijai, Siriporn C Chattipakorn, Nipon Chattipakorn
BACKGROUND: Testosterone deficiency in elderly men increases the risk of cardiovascular disease. In bilateral orchiectomized (ORX) animals, impaired cardiac Ca(2+) regulation was observed, and this impairment could be improved by testosterone replacement, indicating the important role of testosterone in cardiac Ca(2+) regulation. However, the temporal changes of Ca(2+) dyshomeostasis in testosterone-deprived conditions are unclear. Moreover, the effects of early vs. late testosterone replacement are unknown...
November 2017: Cell Calcium
https://www.readbyqxmd.com/read/29018025/peptidyl-prolyl-isomerase-1-regulates-ca-2-handling-by-modulating-sarco-endo-plasmic-reticulum-calcium-atpase-and-na-2-ca-2-exchanger-1-protein-levels-and-function
#16
Veronica Sacchi, Bingyan J Wang, Dieter Kubli, Alexander S Martinez, Jung-Kang Jin, Roberto Alvarez, Nirmala Hariharan, Christopher Glembotski, Takafumi Uchida, James S Malter, Yijun Yang, Polina Gross, Chen Zhang, Steven Houser, Marcello Rota, Mark A Sussman
BACKGROUND: Aberrant Ca(2+) handling is a prominent feature of heart failure. Elucidation of the molecular mechanisms responsible for aberrant Ca(2+) handling is essential for the development of strategies to blunt pathological changes in calcium dynamics. The peptidyl-prolyl cis-trans isomerase peptidyl-prolyl isomerase 1 (Pin1) is a critical mediator of myocardial hypertrophy development and cardiac progenitor cell cycle. However, the influence of Pin1 on calcium cycling regulation has not been explored...
October 10, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28985746/porcine-model-of-progressive-cardiac-hypertrophy-and-fibrosis-with-secondary-postcapillary-pulmonary-hypertension
#17
Mariann Gyöngyösi, Noemi Pavo, Dominika Lukovic, Katrin Zlabinger, Andreas Spannbauer, Denise Traxler, Georg Goliasch, Ljubica Mandic, Jutta Bergler-Klein, Alfred Gugerell, Andras Jakab, Zsuzsanna Szankai, Levente Toth, Rita Garamvölgyi, Gerald Maurer, Frederic Jaisser, Faiez Zannad, Thomas Thum, Sándor Bátkai, Johannes Winkler
BACKGROUND: Meaningful translational large animal models for cardiac diseases are indispensable for studying disease mechanisms, development of novel therapeutic strategies, and evaluation of potential drugs. METHODS: For induction of heart failure, cardiac hypertrophy and fibrosis, a bare metal stent was implanted in the descending aorta of growing pigs (n = 7), inducing pressure stress on the left ventricle (group HYPI). The constant stent size in growing pigs resulted in antegrade partial obstruction of the aortic flow with a gradual increase in afterload...
October 6, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28928601/early-right-ventricular-apical-pacing-induced-gene-expression-alterations-are-associated-with-deterioration-of-left-ventricular-systolic-function
#18
Haiyan Xu, Xiongwei Xie, Jiangjin Li, Yuanyuan Zhang, Changsong Xu, Jing Yang
The chronic high-dose right ventricular apical (RVA) pacing may have deleterious effects on left ventricular (LV) systolic function. We hypothesized that the expression changes of genes regulating cardiomyocyte energy metabolism and contractility were associated with deterioration of LV function in patients who underwent chronic RVA pacing. Sixty patients with complete atrioventricular block and preserved ejection fraction (EF) who underwent pacemaker implantation were randomly assigned to either RVA pacing (n = 30) group or right ventricular outflow tract (RVOT) pacing (n = 30) group...
2017: Disease Markers
https://www.readbyqxmd.com/read/28889229/melatonin-alleviates-inflammation-induced-apoptosis-in-human-umbilical-vein-endothelial-cells-via-suppression-of-ca-2-xo-ros-drp1-mitochondrial-fission-axis-by-activation-of-ampk-serca2a-pathway
#19
Jiasen Cui, Zeng Li, Shunjiu Zhuang, Shaohong Qi, Li Li, Junwen Zhou, Wan Zhang, Yun Zhao
Endothelia inflammation damage is vital to the development and progression of chronic venous disease. In the present study, we explored the protective effect of melatonin on endothelia apoptosis induced by LPS, particularly focusing on the mitochondrial fission. We demonstrated that human umbilical vein endothelial cells (HUVEC) subjected to LPS for 12 h exhibited a higher apoptotic rate. However, melatonin (1-20 μM) treatment 12 h before LPS had the ability to protect HUVEC cell against LPS-mediated apoptosis in a dose-dependent manner...
September 9, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28884444/the-ccaat-box-in-the-proximal-serca2-gene-promoter-regulates-basal-and-stress-induced-transcription-in-cardiomyocytes
#20
Jorge Fragoso-Medina, Gabriela Rodriguez, Angel Zarain-Herzberg
The cardiac sarco/endoplasmic reticulum Ca(2+)-ATPase-2a (SERCA2a) is vital for the correct handling of calcium concentration in cardiomyocytes. Recent studies showed that the induction of endoplasmic reticulum (ER) stress (ERS) with the SERCA2 inhibitor Thapsigargin (Tg) increases the mRNA and protein levels of SERCA2a. The SERCA2 gene promoter contains an ERS response element (ERSE) at position -78 bp that is conserved among species and might transcriptionally regulate SERCA2 gene expression. However, its involvement in SERCA2 basal and calcium-mediated transcriptional activation has not been elucidated...
September 7, 2017: Molecular and Cellular Biochemistry
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