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SERCA2a

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https://www.readbyqxmd.com/read/28578382/astragaloside-iv-alleviates-heart-failure-via-activating-ppar%C3%AE-to-switch-glycolysis-to-fatty-acid-%C3%AE-oxidation
#1
Zhiwei Dong, Pei Zhao, Ming Xu, Chen Zhang, Wei Guo, Huihua Chen, Jing Tian, Hongchang Wei, Rong Lu, Tongtong Cao
In heart failure (HF), energy metabolism pathway in cardiac muscle changes from fatty acid β-oxidation to glycolysis. However, the exact mechanism is unknown. Sarcoendoplasmic reticulum Ca(2+)α ATPase (SERCA) expression is downregulated and mitochondrial function is reduced in HF, perhaps partly due to a substantially reduced energy supply for excitation-contraction coupling resulting from a lower fatty acid β-oxidation rate. We investigated whether Astragaloside IV can activate peroxisome proliferator-activated receptor alpha (PPARα) to stimulate fatty acid β-oxidation and increase cardiac energy production, improving mitochondrial function and the efficiency of SERCA in HF...
June 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28533073/the-impact-of-sevoflurane-on-coupling-of-the-left-ventricular-to-systemic-vasculature-in-rats-with-chronic-pulmonary-hypertension
#2
Lu Wang, Hui Luo, Gang Qin, Yanan Cao, Xiaowei Gao, Zhong Zhang, Zhi Ye, Junjie Zhang, Qulian Guo, E Wang
OBJECTIVES: The relationship between left ventricular function and afterload has not been investigated as much as the right ventricular function under chronic pulmonary hypertension (PH) during anesthesia. This study was designed to investigate effects of sevoflurane on the intrinsic coupling relationship between the left ventricle and systemic vasculature in the presence of PH. DESIGN: A randomized, controlled study. SETTING: University hospital...
February 13, 2017: Journal of Cardiothoracic and Vascular Anesthesia
https://www.readbyqxmd.com/read/28522367/qrs-t-wave-and-calcium-alternans-in-a-type-i-diabetic-mouse-model-for-spontaneous-postmyocardial-infarction-ventricular-tachycardia-a-mechanism-for-the-antiarrhythmic-effect-of-statins
#3
Hongwei Jin, Charles M Welzig, Mark Aronovitz, Farzad Noubary, Robert Blanton, Bo Wang, Mohammad Rajab, Alfred Albano, Mark S Link, Sami F Noujaim, Ho-Jin Park, Jonas B Galper
BACKGROUND: The incidence of sudden arrhythmic death is markedly increased in diabetics. OBJECTIVE: The purpose of this study was to develop a mouse model for postmyocardial infarction (post-MI) ventricular tachycardia (VT) in the diabetic heart and determine the mechanism of an antiarrhythmic effect of statins. METHODS: ECG transmitters were implanted in wild-type (WT), placebo, and pravastatin-treated type I diabetic Akita mice. MIs were induced by coronary ligation, and Ca(2+) transients were studied by optical mapping, and Ca(2+) transients and sparks in left ventricular myocytes (VM) by the Ionoptix system and confocal microscopy...
May 15, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28514771/istaroxime-a-potential-anticancer-drug-in-prostate-cancer-exerts-beneficial-functional-effects-in-healthy-and-diseased-human-myocardium
#4
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/28509762/beetroot-juice-increases-human-muscle-force-without-changing-ca2-handling-proteins
#5
Jamie Whitfield, Daniel Gamu, George J F Heigenhauser, Luc J C van Loon, Lawrence L Spriet, A Russell Tupling, Graham P Holloway
Dietary inorganic nitrate (NO3) supplementation improves skeletal muscle (SkM) contractile efficiency, and while rodent literature has suggested improvements in calcium handling or redox modifications as likely explanations, the direct mechanism-of-action in humans remains unknown. PURPOSE: To examine the effects of 7-d of beetroot juice (BRJ) supplementation on SkM contractile characteristics and function. METHODS: Recreationally active males (n=8) underwent transcutaneous electrical muscle stimulation of the vastus lateralis for evaluation of contractile characteristics before (pre) and after (post) 7-d of BRJ supplementation (280 mL/day, ~26 mmol NO3)...
May 15, 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/28497395/cardio-protective-effects-of-qishen-granule-on-sarcoplasmic-reticulum-ca-2-handling-in-heart-failure-rats
#6
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/28490840/toll-like-receptor-9-promotes-survival-in-serca2a-ko-heart-failure-mice
#7
Yangchen Dhondup, Ivar Sjaastad, Øystein Sandanger, Jan Magnus Aronsen, Muhammad Shakil Ahmed, Håvard Attramadal, Alexandra Vanessa Finsen, Lili Zhang, Trine Ranheim, Katrine Alfsnes, Pål Aukrust, Geir Christensen, Arne Yndestad, Leif Erik Vinge
Aim. Inflammation is important in heart failure (HF). The role of the immune receptor toll-like receptor 9 (TLR9) in HF is not understood and not investigated in diastolic HF. We investigated the role of TLR9 in a murine diastolic HF model caused by cardiomyocyte SERCA2a excision. Methods and Results. We crossed SERCA2a KO and TLR9 KO mice to generate four mouse lines. Tamoxifen-induced cardiomyocyte SERCA2a gene excision was carried out in mice, causing diastolic HF. After 7.6 weeks, cardiac functions and dimensions were analyzed by echocardiography and heart tissues were processed...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28439258/diabetic-cardiomyopathy-an-immunometabolic-perspective
#8
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/28423119/importance-of-serca2a-on-early-isolated-diastolic-dysfunction-induced-by-supravalvular-aortic-stenosis-in-rats
#9
C F S M P Silveira, D H S Campos, P P Freire, A F Deus, K Okoshi, C R Padovani, A C Cicogna
Cardiac remodeling is defined as changes in shape and function of the heart in response to aggression (pressure overload). The sarcoplasmic reticulum calcium ATPase cardiac isoform 2a (SERCA2a) is a known factor that influences function. A wide spectrum of studies report a decrease in SERCA2a in heart failure, but none evaluate it's the role in early isolated diastolic dysfunction in supravalvular aortic stenosis (AoS). Our hypothesis was that SERCA2a participates in such dysfunction. Thirty-day-old male Wistar rats (60-80 g) were divided into AoS and Sham groups, which were submitted to surgery with or without aorta clipping, respectively...
April 13, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28398363/-gene-therapy-in-heart-failure-the-unexpected-results-from-the-cupid-2-trial
#10
Marta Gigli, Gianfranco Sinagra, Luisa Mestroni
Heart failure is still a major cause of morbidity and mortality in Europe and North America. In the last three decades, gene therapy emerged as a target in the molecular mechanisms implicated in heart failure encouraging preclinical gene therapy studies in small and large animal models. Prior studies documented a decreased expression of sarcoplasmic reticulum Ca2+-ATPase protein (SERCA2a), a major cardiac calcium cycling protein, in heart failure. These results paved the way to preliminary studies based on gene transfer strategies of SERCA2a...
February 2017: Giornale Italiano di Cardiologia
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
#11
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
https://www.readbyqxmd.com/read/28384221/kchip2-regulates-the-cardiac-ca2-transient-and-myocyte-contractility-by-targeting-ryanodine-receptor-activity
#12
Drew M Nassal, Xiaoping Wan, Haiyan Liu, Kenneth R Laurita, Isabelle Deschênes
Pathologic electrical remodeling and attenuated cardiac contractility are featured characteristics of heart failure. Coinciding with these remodeling events is a loss of the K+ channel interacting protein, KChIP2. While, KChIP2 enhances the expression and stability of the Kv4 family of potassium channels, leading to a more pronounced transient outward K+ current, Ito,f, the guinea pig myocardium is unique in that Kv4 expression is absent, while KChIP2 expression is preserved, suggesting alternative consequences to KChIP2 loss...
2017: PloS One
https://www.readbyqxmd.com/read/28380414/the-role-of-sirt1-in-diabetic-cardiomyopathy
#13
REVIEW
Hedyieh Karbasforooshan, Gholamreza Karimi
The prevalence of diabetes mellitus (DM) has been increasing worldwide. Diabetic cardiomyopathy (DCP) is the major risk for diabetes associated morbidity and mortality. Hyperglycemia and hyperinsulinemia play an indispensable role in underlying mechanisms of DCP. They increase advanced glycation end products (AGEs) following a series of events leading to myocardial damage and cardiomyopathy which include oxidative stress, increased inflammation, fibrosis, hypertrophy and apoptosis. SIRT1 is a nicotinamide adenosine dinucleotide (NAD)-dependent deacetylase that removes acetyl groups from proteins which can be implicated in DCP...
June 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28370799/through-modulation-of-cardiac-ca-2-handling-ucp2-affects-cardiac-electrophysiology-and-influences-the-susceptibility-for-ca-2-mediated-arrhythmias
#14
Robert Larbig, Sara Reda, Vera Paar, Andrea Trost, Johannes Leitner, Stephanie Weichselbaumer, Karolina A Motloch, Bernhard Wernly, Andreas Arrer, Benjamin Strauss, Michael Lichtenauer, Herbert A Reitsamer, Lars Eckardt, Guiscard Seebohm, Uta C Hoppe, Lukas J Motloch
Introduction UCP2 belongs to a superfamily of mitochondrial ion transporters. Due to its beneficial influence on production of reactive oxygen species it is suggested to reduce cardiac ischemic reperfusion injury. Recent studies uncovered its ability to regulate mitochondrial Ca(2+) -uptake and therefore to influence cardiac cytosolic Ca(2+) -handling, indicating compensatory pathways to avoid toxic Ca(2+) -overload in UCP2 knock-out mice (UCP2(-/-) ). However, the specific mechanisms and their impact on cardiac electrophysiology remain speculative...
March 31, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28322590/randomized-clinical-trials-of-gene-transfer-for-heart-failure-with-reduced-ejection-fraction
#15
William F Penny, H Kirk Hammond
Despite improvements in drug and device therapy for heart failure, hospitalization rates and mortality have changed little in the past decade. Randomized clinical trials using gene transfer to improve function of the failing heart are the focus of this review. Four randomized clinical trials of gene transfer in heart failure with reduced ejection fraction (HFrEF) have been published. Each enrolled patients with stable symptomatic HFrEF and used either intracoronary delivery of a virus vector or endocardial injection of a plasmid...
May 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28270843/liraglutide-directly-protects-cardiomyocytes-against-reperfusion-injury-possibly-via-modulation-of-intracellular-calcium-homeostasis
#16
Shun-Ying Hu, Ying Zhang, Ping-Jun Zhu, Hao Zhou, Yun-Dai Chen
BACKGROUND: Liraglutide is glucagon-like peptide-1 receptor agonist for treating patients with type 2 diabetes mellitus. Our previous studies have demonstrated that liraglutide protects cardiac function through improving endothelial function in patients with acute myocardial infarction undergoing percutaneous coronary intervention. The present study will investigate whether liraglutide can perform direct protective effects on cardiomyocytes against reperfusion injury. METHODS: In vitro experiments were performed using H9C2 cells and neonatal rat ventricular cadiomyocytes undergoing simulative hypoxia/reoxygenation (H/R) induction...
January 2017: Journal of Geriatric Cardiology: JGC
https://www.readbyqxmd.com/read/28242257/exendin-4-inhibits-structural-remodeling-and-improves-ca-2-homeostasis-in-rats-with-heart-failure-via-the-glp-1-receptor-through-the-enos-cgmp-pkg-pathway
#17
Jingjing Chen, Dandan Wang, Fangai Wang, Shaobo Shi, Yuting Chen, Bo Yang, Yanhong Tang, Congxin Huang
The glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 is a long-acting analog of GLP-1, which stimulates insulin secretion and is clinically used in the treatment of type 2 diabetes. Previous studies have demonstrated that GLP-1 agonists and analogs serve as cardioprotective factors in various conditions. Disturbances in calcium cycling are characteristic of heart failure (HF); therefore, the aim of this study was to investigate the effect of exendin-4 (a GLP-1 mimetic) on the regulation of calcium handling and to identify the underlying mechanisms in an HF rat model after myocardial infarction (MI)...
April 2017: Peptides
https://www.readbyqxmd.com/read/28223472/overexpression-of-sarcoendoplasmic-reticulum-calcium-atpase-2a-promotes-cardiac-sympathetic-neurotransmission-via-abnormal-endoplasmic-reticulum-and-mitochondria-ca-2-regulation
#18
Julia Shanks, Neil Herring, Errin Johnson, Kun Liu, Dan Li, David J Paterson
Reduced cardiomyocyte excitation-contraction coupling and downregulation of the SERCA2a (sarcoendoplasmic reticulum calcium ATPase 2a) is associated with heart failure. This has led to viral transgene upregulation of SERCA2a in cardiomyocytes as a treatment. We hypothesized that SERCA2a gene therapy expressed under a similar promiscuous cytomegalovirus promoter could also affect the cardiac sympathetic neural axis and promote sympathoexcitation. Stellate neurons were isolated from 90 to 120 g male, Sprague-Dawley, Wistar Kyoto, and spontaneously hypertensive rats...
April 2017: Hypertension
https://www.readbyqxmd.com/read/28222421/luteolin-enhances-sarcoplasmic-reticulum-ca2-atpase-activity-through-p38-mapk-signaling-thus-improving-rat-cardiac-function-after-ischemia-reperfusion
#19
Shasha Zhu, Tongda Xu, Yuanyuan Luo, Yingying Zhang, Haochen Xuan, Yanfeng Ma, Defeng Pan, Dongye Li, Hong Zhu
BACKGROUND/AIMS: A major challenge for current therapeutic strategies against ischemia/reperfusion (I/R) is the lack of effective drugs. Considering luteolin enhances the activity of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) to improve the systolic/diastolic function of rat hearts and cardiomyocytes during the I/R process, we studied the regulatory function of the p38 MAPK pathway in this protective mechanism. METHODS: Isolated cardiomyocytes and perfused hearts were separately divided into five groups and used to investigate I/R...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28218221/gene-expressions-underlying-mishandled-calcium-clearance-and-elevated-generation-of-reactive-oxygen-species-in-the-coronary-artery-smooth-muscle-cells-of-chronic-heart-failure-rats
#20
Liang Ding, Xian-Xiu Su, Wen-Hui Zhang, Yu-Xiang Xu, Xue-Feng Pan
BACKGROUND: The calcium clearance and reactive oxygen species (ROS) generations in the coronary artery smooth muscle cells in chronic heart failure (HF) have not been fully investigated. Therefore, we attempted to understand the gene expressions underlying the mishandling of calcium clearance and the accumulations of ROS. METHODS: We initially established an animal model of chronic HF by making the left anterior descending coronary artery ligation (CAL) in rats, and then isolated the coronary artery vascular smooth muscle cells from the ischemic and the nonischemic parts of the coronary artery vessels in 12 weeks after CAL operation...
February 20, 2017: Chinese Medical Journal
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