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(SERCA* OR "sarcoplasmic reticulum Ca2+ ATPase") AND heart

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https://www.readbyqxmd.com/read/29753687/istaroxime-a-positive-inotropic-agent-devoid-of-proarrhythmic-properties-in-sensitive-chronic-atrioventricular-block-dogs
#1
Alexandre Bossu, Amée Kostense, Henriette D M Beekman, Marien J C Houtman, Marcel A G van der Heyden, Marc A Vos
Current inotropic agents in heart failure therapy associate with low benefit and significant adverse effects, including ventricular arrhythmias. Istaroxime, a novel Na+ /K+ -transporting ATPase inhibitor, also stimulates SERCA2a activity, which would confer improved inotropic and lusitropic properties with less proarrhythmic effects. We investigated hemodynamic, electrophysiological and potential proarrhythmic and antiarrhythmic effects of istaroxime in control and chronic atrioventricular block (CAVB) dogs sensitive to drug-induced Torsades de Pointes arrhythmias (TdP)...
May 10, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29748131/underlying-mechanism-of-the-contractile-dysfunction-in-atrophied-ventricular-myocytes-from-a-murine-model-of-hypothyroidism
#2
Dolores Montalvo, Perla Pérez-Treviño, Katheryne Madrazo-Aguirre, Fabio A González-Mondellini, Hipólito O Miranda-Roblero, Diego Ramonfaur-Gracia, Mariana Jacobo-Antonio, Maritza Mayorga-Luna, Norma L Gómez-Víquez, Noemí García, Julio Altamirano
Hypothyroidism (Hypo) is a risk factor for cardiovascular diseases, including heart failure. Hypo rapidly induces Ca2+ mishandling and contractile dysfunction (CD), as well as atrophy and ventricular myocytes (VM) remodeling. Hypo decreases SERCA-to-phospholamban ratio (SERCA/PLB), and thereby contributes to CD. Nevertheless, detailed spatial and temporal Ca2+ cycling characterization in VM is missing, and contribution of other structural and functional changes to the mechanism underlying Ca2+ mishandling and CD, as transverse tubules (T-T) remodeling, mitochondrial density (Dmit ) and energy availability, is unclear...
February 5, 2018: Cell Calcium
https://www.readbyqxmd.com/read/29748130/effects-of-the-iron-chelator-deferiprone-and-the-t-type-calcium-channel-blocker-efonidipine-on-cardiac-function-and-ca-2-regulation-in-iron-overloaded-thalassemic-mice
#3
Juthamas Khamseekaew, Sirinart Kumfu, Siripong Palee, Suwakon Wongjaikam, Somdet Srichairatanakool, Suthat Fucharoen, Siriporn C Chattipakorn, Nipon Chattipakorn
Although disturbance of cardiac Ca2+ regulation is involved in the pathophysiology of iron-overload cardiomyopathy, the obvious mechanisms involved in the dysregulation of iron-induced cardiac Ca2+ are unclear. Moreover, the roles of the iron chelator deferiprone and the T-type calcium channel blocker efonidipine on cardiac intracellular Ca2+ transients and Ca2+ regulatory proteins in thalassemic mice are still unknown. We tested the hypothesis that treatment with either deferiprone or efonidipine attenuated cardiac Ca2+ dysregulation and led to improved left ventricular (LV) function in iron-overloaded thalassemic mice...
February 6, 2018: Cell Calcium
https://www.readbyqxmd.com/read/29727991/co-exposure-of-silica-nanoparticles-and-methylmercury-induced-cardiac-toxicity-in-vitro-and-in-vivo
#4
Xiaozhe Yang, Lin Feng, Yannan Zhang, Hejing Hu, Yanfeng Shi, Shuang Liang, Tong Zhao, Lige Cao, Junchao Duan, Zhiwei Sun
The released nanoparticles into environment can potentially interact with pre-existing pollution, maybe causing higher toxicity. As such, assessment of their joint toxic effects is necessary. This study was to investigate the co-exposure cardiac toxicity of silica nanoparticles (SiNPs) and methylmercury (MeHg). Factorial design was used to determine the potential joint action type. In vitro study, human cardiomyocytes (AC16) were exposed to SiNPs and MeHg alone or the combination. Higher toxicity was observed on cell viability, cell membrane damage in co-exposure compared with single exposure and control...
August 1, 2018: Science of the Total Environment
https://www.readbyqxmd.com/read/29723491/qsox1-a-novel-actor-of-cardiac-protection-upon-acute-stress-in-mice
#5
Anais Caillard, Malha Sadoune, Arthur Cescau, Mehdi Meddour, Marine Gandon, Evelyne Polidano, Claude Delcayre, Kelly Da Silva, Philippe Manivet, Ana-Maria Gomez, Alain Cohen-Solal, Nicolas Vodovar, Zhenlin Li, Alexandre Mebazaa, Jane-Lise Samuel
QSOX1, a sulfhydryl oxidase, was shown to be upregulated in the heart upon acute heart failure (AHF). The aim of the study was to unravel QSOX1 roles during AHF. We generated and characterized mice with QSOX1 gene deletion. The QSOX1-/- mice were viable but adult male exhibited a silent dilated cardiomyopathy. The QSOX1-/- hearts were characterized by low protein SERCA2a levels associated with a calcium homeostasis alteration, high levels of the endoplasmic reticulum (ER) chaperone proteins Grp78/Bip, and of the ER apoptosis sensor CHOP, indicating a chronic unfolded protein response (UPR)...
April 30, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29696147/drug-interactions-with-the-ca-2-atpase-from-sarco-endo-plasmic-reticulum-serca
#6
REVIEW
Francesco Tadini-Buoninsegni, Serena Smeazzetto, Roberta Gualdani, Maria Rosa Moncelli
The sarco(endo)plasmic reticulum Ca2+ -ATPase (SERCA) is an intracellular membrane transporter that utilizes the free energy provided by ATP hydrolysis for active transport of Ca2+ ions from the cytoplasm to the lumen of sarco(endo)plasmic reticulum. SERCA plays a fundamental role for cell calcium homeostasis and signaling in muscle cells and also in cells of other tissues. Because of its prominent role in many physiological processes, SERCA dysfunction is associated to diseases displaying various degrees of severity...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29686704/the-change-of-left-ventricular-function-in-rats-with-subclinical-hypothyroid-and-the-effects-of-thyroxine-replacement
#7
Xuedi Chen, Cuixia Gao, Ningning Gong, Yu Wang, Limin Tian
Objective: The main purpose of this study was to explore the relationships between serca2a, Ryr2, adipokines, and the left ventricular function in the subclinical hypothyroidism with different TSH levels and to determine the impact of L-T4 treatment on these indexes. Methods: Sixty-five male Wistar rats were randomly divided into five groups: control group; sHT A, B, and C group; and sHT + T4 group. The sHT rats were induced by methimazole (MMI), and the sHT + T4 rats were administered with L-T4 treatment after 8 weeks of MMI administration...
2018: International Journal of Endocrinology
https://www.readbyqxmd.com/read/29674140/impaired-ca-2-cycling-of-nonischemic-myocytes-contributes-to-sarcomere-dysfunction-early-after-myocardial-infarction
#8
Annette Kronenbitter, Florian Funk, Katarzyna Hackert, Simone Gorreßen, Dennis Glaser, Peter Boknik, Gereon Poschmann, Kai Stühler, Malgorzata Isić, Martina Krüger, Joachim P Schmitt
Changes in the nonischemic remote myocardium of the heart contribute to left ventricular dysfunction after ischemia and reperfusion (I/R). Understanding the underlying mechanisms early after I/R is crucial to improve the adaptation of the viable myocardium to increased mechanical demands. Here, we investigated the role of myocyte Ca2+ handling in the remote myocardium 24 h after 60 min LAD occlusion. Cardiomyocytes isolated from the basal noninfarct-related parts of wild type mouse hearts demonstrated depressed beat-to-beat Ca2+ handling...
April 16, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29670896/short-term-treatment-with-esmolol-reverses-left-ventricular-hypertrophy-in-adult-spontaneously-hypertensive-rats-via-inhibition-of-akt-nf-%C3%AE%C2%BA-b-and-nfatc4
#9
Begoña Quintana-Villamandos, David A Goukassian, Sharath P Sasi, Emilio Delgado-Baeza
Our group has previously demonstrated that short-term treatment with esmolol reduces left ventricular hypertrophy (LVH) in spontaneously hypertensive rats (SHRs). The present study aimed to assess the molecular mechanisms related to this effect. Fourteen-month-old male SHRs were treated intravenously with saline as vehicle (SHR) or esmolol (SHR-E) (300  μ g/kg/min). Age-matched vehicle-treated male Wistar-Kyoto (WKY) rats served as controls. After 48 hours of treatment, the hearts were harvested and left ventricular tissue was separated and processed for Western blot analysis to determine the levels of Akt, NF- κ B, NFATc4, Creb1, Serca2a, Erk1/2, and Sapk/Jnk...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29621141/correcting-calcium-dysregulation-in-chronic-heart-failure-using-serca2a-gene-therapy
#10
REVIEW
T Jake Samuel, Ryan P Rosenberry, Seungyong Lee, Zui Pan
Chronic heart failure (CHF) is a major contributor to cardiovascular disease and is the leading cause of hospitalization for those over the age of 65, which is estimated to account for close to seventy billion dollars in healthcare costs by 2030 in the US alone. The successful therapies for preventing and reversing CHF progression are urgently required. One strategy under active investigation is to restore dysregulated myocardial calcium (Ca2+ ), a hallmark of CHF. It is well established that intracellular Ca2+ concentrations are tightly regulated to control efficient myocardial systolic contraction and diastolic relaxation...
April 5, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29604965/computational-modeling-of-amylin-induced-calcium-dysregulation-in-rat-ventricular-cardiomyocytes
#11
Bradley D Stewart, Caitlin E Scott, Thomas P McCoy, Guo Yin, Florin Despa, Sanda Despa, Peter M Kekenes-Huskey
Hyperamylinemia is a condition that accompanies obesity and precedes type II diabetes, and it is characterized by above-normal blood levels of amylin, the pancreas-derived peptide. Human amylin oligomerizes easily and can deposit in the pancreas [1], brain [2], and heart [3], where they have been associated with calcium dysregulation. In the heart, accumulating evidence suggests that human amylin oligomers form moderately cation-selective [4,5] channels that embed in the cell sarcolemma (SL). The oligomers increase membrane conductance in a concentration-dependent manner [5], which is correlated with elevated cytosolic Ca2+ ...
May 2018: Cell Calcium
https://www.readbyqxmd.com/read/29601906/melatonin-therapy-for-diabetic-cardiomyopathy-a-mechanism-involving-syk-mitochondrial-complex-i-serca-pathway
#12
Hao Zhou, Yan Yue, Jin Wang, Qiang Ma, Yundai Chen
Melatonin and its metabolites have been demonstrated to modulate the glucose, dyslipidemia and other metabolic disorders. This study aimed to explore a novel mechanism responsible for diabetic cardiomyopathy development, and also validated whether melatonin played a protective role in repairing damaged heart in the diabetes setting. Our data demonstrated that spleen tyrosine kinase (Syk) was activated by chronic high-glucose stimulus and contributed to the development of diabetic cardiomyopathy. However, genetic ablation of Syk or supplementation of melatonin to inhibit Syk activation improved diabetic myocardial function, reduced cardiac fibrosis and preserved cardiomyocytes viability...
July 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29550715/cardiometabolic-response-of-juvenile-rainbow-trout-exposed-to-dietary-selenomethionine
#13
Connor M Pettem, Jennifer M Briens, David M Janz, Lynn P Weber
Selenium (Se) is considered an essential trace element, involved in important physiological and metabolic functions for all vertebrate species. Fish require dietary concentrations of 0.1-0.5 μg Se/g dry mass (d.m.) to maintain normal physiological and selenoprotein function, however concentrations exceeding 3 μg/g d.m. have been shown to cause toxicity. As Se is reported to have a narrow margin between essentiality and toxicity, there is growing concern surrounding the adverse effects of elevated Se exposure caused by anthropogenic activities...
March 8, 2018: Aquatic Toxicology
https://www.readbyqxmd.com/read/29518932/diazoxide-improves-mitochondrial-connexin-43-expression-in-a-mouse-model-of-doxorubicin-induced-cardiotoxicity
#14
Michela Pecoraro, Michele Ciccarelli, Antonella Fiordelisi, Guido Iaccarino, Aldo Pinto, Ada Popolo
Doxorubicin (DOXO) administration induces alterations in Connexin 43 (Cx43) expression and localization, thus, inducing alterations in chemical and electrical signal transmission between cardiomyocytes and in intracellular calcium homeostasis even evident after a single administration. This study was designed to evaluate if Diazoxide (DZX), a specific opener of mitochondrial KATP channels widely used for its cardioprotective effects, can fight DOXO-induced cardiotoxicity in a short-time mouse model. DZX (20 mg/kg i...
March 7, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29501609/effects-of-the-arg9cys-and-arg25cys-mutations-on-phospholamban-s-conformational-equilibrium-in-membrane-bilayers
#15
Sarah E D Nelson, Kim N Ha, Tata Gopinath, Mara H Exline, Alessandro Mascioni, David D Thomas, Gianluigi Veglia
Approximately, 70% of the Ca2+ ion transport into the sarcoplasmic reticulum is catalyzed by the sarcoplasmic reticulum Ca2+ -ATPase (SERCA), whose activity is endogenously regulated by phospholamban (PLN). PLN comprises a TM inhibitory region and a cytoplasmic regulatory region that harbors a consensus sequence for cAMP-dependent protein kinase (PKA). The inhibitory region binds the ATPase, reducing its apparent Ca2+ binding affinity. β-adrenergic stimulation activates PKA, which phosphorylates PLN at Ser 16, reversing its inhibitory function...
June 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29478009/new-insights-into-serca2a-gene-therapy-in-heart-failure-pay-attention-to-the-negative-effects-of-b-type-natriuretic-peptides
#16
Yuting Zhai, Yuanyuan Luo, Pei Wu, Dongye Li
Sarcoplasmic/endoplasmic reticulum calcium ATPase 2a (SERCA2a) is a target of interest in gene therapy for heart failure with reduced ejection fraction (HFrEF). However, the results of an important clinical study, the Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID) trial, were controversial. Promising results were observed in the CUPID 1 trial, but the results of the CUPID 2 trial were negative. The factors that caused the controversial results remain unclear. Importantly, enrolled patients were required to have a higher plasma level of B-type natriuretic peptide (BNP) in the CUPID 2 trial...
May 2018: Journal of Medical Genetics
https://www.readbyqxmd.com/read/29475982/lncrna-zfas1-as-a-serca2a-inhibitor-to-cause-intracellular-ca-2-overload-and-contractile-dysfunction-in-a-mouse-model-of-myocardial-infarction
#17
Ying Zhang, Lei Jiao, Lihua Sun, Yanru Li, Yuqiu Gao, Chaoqian Xu, Yingchun Shao, Mengmeng Li, Chunyan Li, Yanjie Lu, Zhenwei Pan, Lina Xuan, Yiyuan Zhang, Qingqi Li, Rui Yang, Yuting Zhuang, Yong Zhang, Baofeng Yang
RATIONALE: Ca2+ homeostasis-a critical determinant of cardiac contractile function-is critically regulated by SERCA2a (sarcoplasmic reticulum Ca2+ -ATPase 2a). Our previous study has identified ZFAS1 as a new lncRNA biomarker of acute myocardial infarction (MI). OBJECTIVE: To evaluate the effects of ZFAS1 on SERCA2a and the associated Ca2+ homeostasis and cardiac contractile function in the setting of MI. METHODS AND RESULTS: ZFAS1 expression was robustly increased in cytoplasm and sarcoplasmic reticulum in a mouse model of MI and a cellular model of hypoxia...
May 11, 2018: Circulation Research
https://www.readbyqxmd.com/read/29450407/changes-in-the-cardiac-ghsr1a-ghrelin-system-correlate-with-myocardial-dysfunction-in-diabetic-cardiomyopathy-in-mice
#18
Rebecca Sullivan, Rebecca McGirr, Shirley Hu, Alice Tan, Derek Wu, Carlie Charron, Tyler Lalonde, Edith Arany, Subrata Chakrabarti, Leonard Luyt, Savita Dhanvantari
Ghrelin and its receptor, the growth hormone secretagogue receptor 1a (GHSR1a), are present in cardiac tissue. Activation of GHSR1a by ghrelin promotes cardiomyocyte contractility and survival, and changes in myocardial GHSR1a and circulating ghrelin track with end-stage heart failure, leading to the hypothesis that GHSR1a is a biomarker for heart failure. We hypothesized that GHSR1a could also be a biomarker for diabetic cardiomyopathy (DCM). We used two models of streptozotocin (STZ)-induced DCM: group 1, adult mice treated with 35 mg/kg STZ for 3 days; and group 2, neonatal mice treated with 70 mg/kg STZ at days 2 and 5 after birth...
February 1, 2018: Journal of the Endocrine Society
https://www.readbyqxmd.com/read/29449318/exosomal-microrna-21-5p-mediates-mesenchymal-stem-cell-paracrine-effects-on-human-cardiac-tissue-contractility
#19
Joshua Mayourian, Delaine K Ceholski, Przemek A Gorski, Prabhu Mathiyalagan, Jack F Murphy, Sophia I Salazar, Francesca Stillitano, Joshua M Hare, Susmita Sahoo, Roger J Hajjar, Kevin D Costa
RATIONALE: The promising clinical benefits of delivering human mesenchymal stem cells (hMSCs) for treating heart disease warrant a better understanding of underlying mechanisms of action. hMSC exosomes increase myocardial contractility; however, the exosomal cargo responsible for these effects remains unresolved. OBJECTIVE: This study aims to identify lead cardioactive hMSC exosomal microRNAs to provide a mechanistic basis for optimizing future stem cell-based cardiotherapies...
March 30, 2018: Circulation Research
https://www.readbyqxmd.com/read/29431258/human-cardiomyocyte-calcium-handling-and-transverse-tubules-in-mid-stage-of-post-myocardial-infarction-heart-failure
#20
Morten Andre Høydal, Idar Kirkeby-Garstad, Asbjørn Karevold, Rune Wiseth, Rune Haaverstad, Alexander Wahba, Tomas L Stølen, Riccardo Contu, Gianluigi Condorelli, Øyvind Ellingsen, Godfrey L Smith, Ole J Kemi, Ulrik Wisløff
AIMS: Cellular processes in the heart rely mainly on studies from experimental animal models or explanted hearts from patients with terminal end-stage heart failure (HF). To address this limitation, we provide data on excitation contraction coupling, cardiomyocyte contraction and relaxation, and Ca2+ handling in post-myocardial-infarction (MI) patients at mid-stage of HF. METHODS AND RESULTS: Nine MI patients and eight control patients without MI (non-MI) were included...
February 12, 2018: ESC Heart Failure
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