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

Uros Kuzmanov, Hongbo Guo, Diana Buchsbaum, Jake Cosme, Cynthia Abbasi, Ruth Isserlin, Parveen Sharma, Anthony O Gramolini, Andrew Emili
Phospholamban (PLN) plays a central role in Ca(2+) homeostasis in cardiac myocytes through regulation of the sarco(endo)plasmic reticulum Ca(2+)-ATPase 2A (SERCA2A) Ca(2+) pump. An inherited mutation converting arginine residue 9 in PLN to cysteine (R9C) results in dilated cardiomyopathy (DCM) in humans and transgenic mice, but the downstream signaling defects leading to decompensation and heart failure are poorly understood. Here we used precision mass spectrometry to study the global phosphorylation dynamics of 1,887 cardiac phosphoproteins in early affected heart tissue in a transgenic R9C mouse model of DCM compared with wild-type littermates...
October 14, 2016: Proceedings of the National Academy of Sciences of the United States of America
Fábio V G Campanha, Denise Perone, Dijon H S de Campos, Renata de A M Luvizotto, Maria T De Síbio, Miriane de Oliveira, Regiane M C Olimpio, Fernanda C F Moretto, Carlos R Padovani, Gláucia M F S Mazeto, Antonio C Cicogna, Célia R Nogueira
Objective: The current study was aimed at analyzing sarcoplasmic reticulum Ca2+ ATPase (Serca2) and ryanodine receptor type 2 (Ryr2) gene expression in rats subjected to surgery that induced HF and were subsequently treated with T4 using physiological doses. Materials and methods: HF was induced in 18 male Wistar rats by clipping the ascending thoracic aorta to generate aortic stenosis (HFS group), while the control group (9-sham) underwent thoracotomy. After 21 weeks, the HFS group was subdivided into two subgroups...
October 10, 2016: Archives of Endocrinology and Metabolism
Joachim Behar, Ambhighainath Ganesan, Jin Zhang, Yael Yaniv
Sinoatrial nodal cells (SANCs) generate spontaneous action potentials (APs) that control the cardiac rate. The brain modulates SANC automaticity, via the autonomic nervous system, by stimulating membrane receptors that activate (adrenergic) or inactivate (cholinergic) adenylyl cyclase (AC). However, these opposing afferents are not simply additive. We showed that activation of adrenergic signaling increases AC-cAMP/PKA signaling, which mediates the increase in the SANC AP firing rate (i.e., positive chronotropic modulation)...
2016: Frontiers in Physiology
Felix Hohendanner, Jaime DeSantiago, Frank R Heinzel, Lothar A Blatter
We tested the hypothesis that in atrial myocytes from a rabbit left ventricular heart failure (HF) model, spatial inhomogeneity and temporal dyssynchrony of Ca removal during excitation-contraction coupling together with increased Na/Ca exchange (NCX) activity generates a substrate for proarrhythmic Ca release. Ca removal occurs via Ca reuptake into the sarcoplasmic reticulum and extrusion via NCX exclusively in the cell periphery since rabbit atrial myocytes lack transverse tubules. Ca removal kinetics were assessed by the time constant τ of decay of local peripheral subsarcolemmal (SS) and central (CT) action potential (AP) induced Ca transients (CaTs) recorded in confocal line scan mode (using Fluo-4)...
September 30, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Zhe Tian, Keishi Miyata, Tsuyoshi Kadomatsu, Haruki Horiguchi, Hiroyuki Fukushima, Shugo Tohyama, Yoshihiro Ujihara, Takahiro Okumura, Satoshi Yamaguchi, Jiabin Zhao, Motoyoshi Endo, Jun Morinaga, Michio Sato, Taichi Sugizaki, Shunshun Zhu, Kazutoyo Terada, Hisashi Sakaguchi, Yoshihiro Komohara, Motohiro Takeya, Naoki Takeda, Kimi Araki, Ichiro Manabe, Keiichi Fukuda, Kinya Otsu, Jun Wada, Toyoaki Murohara, Satoshi Mohri, Jun K Yamashita, Motoaki Sano, Yuichi Oike
A cardioprotective response that alters ventricular contractility or promotes cardiomyocyte enlargement occurs with increased workload in conditions such as hypertension. When that response is excessive, pathological cardiac remodelling occurs, which can progress to heart failure, a leading cause of death worldwide. Mechanisms underlying this response are not fully understood. Here, we report that expression of angiopoietin-like protein 2 (ANGPTL2) increases in pathologically-remodeled hearts of mice and humans, while decreased cardiac ANGPTL2 expression occurs in physiological cardiac remodelling induced by endurance training in mice...
September 28, 2016: Nature Communications
Lale Tokgözoğlu, Sercan Okutucu, Ergun Barış Kaya, Çetin Erol, Oktay Ergene
OBJECTIVE: The present objective was to compare changes in lifestyle between (i) Turkish women and Turkish men, and (ii) Turkish women and European women, after hospitalization for coronary heart disease (CHD). Risk factor management, physical activity, mood, and quality of life (QOL) indices were compared. METHODS: A total of 2268 women (25.3% of 8966 patients, mean age: 65.8±9.0 years) were interviewed using the European Action on Secondary and Primary Prevention by Intervention to Reduce Events III (EUROASPIRE III)...
September 2016: Türk Kardiyoloji Derneği Arşivi: Türk Kardiyoloji Derneğinin Yayın Organıdır
Haibin Gong, Yanfei Li, Lei Wang, Qian Lv, Xiuli Wang
The study was conducted to examine the effects of ICI 118,551 on the systolic function of cardiac muscle cells of rats in heart failure and determine the molecular mechanism of selective β2-adrenergic receptor (β2-AR) antagonist on these cells. The chronic heart failure model for rats was prepared through abdominal aortic constriction and separate cardiac muscle cells using the collagenase digestion method. The rats were then divided into Sham, HF and HF+ICI 50 nM goups and cultivated for 48 h. β2-AR, Gi/Gs and sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) protein expression levels in the cardiac muscle cells were evaluated by western blotting and changes in the systolic function of cardiac muscle cells based on the boundary detection system of contraction dynamics for individual cells was measured...
September 2016: Experimental and Therapeutic Medicine
Sen Zhu, Rakeshwar S Guleria, Candice M Thomas, Amanda Roth, F N U Gerilechaogetu, Rajesh Kumar, David E Dostal, Kenneth M Baker, Jing Pan
Retinoic acid receptor (RAR) has been implicated in pathological stimuli-induced cardiac remodeling. To determine whether the impairment of RARα signaling directly contributes to the development of heart dysfunction and the involved mechanisms, tamoxifen-induced myocardial specific RARα deletion (RARαKO) mice were utilized. Echocardiographic and cardiac catheterization studies showed significant diastolic dysfunction after 16 wks of gene deletion. However, no significant differences were observed in left ventricular ejection fraction (LVEF), between RARαKO and wild type (WT) control mice...
August 15, 2016: Journal of Molecular and Cellular Cardiology
Chen Lin, Yi-Chung Chang, Ya-Chen Cheng, Po-Jung Lai, Chien-Hung Yeh, Wan-Hsin Hsieh, Kun Hu, June-Tai Wu, Hsiu-Hsiang Lee, Men-Tzung Lo, Yi-Lwun Ho
Judiciously tuning heart rates is critical for regular cardiovascular function. The fractal pattern of heartbeats - a multiscale regulation in instantaneous fluctuations - is well known for vertebrates. The most primitive heart system of the Drosophila provides a useful model to understand the evolutional origin of such a fractal pattern as well as the alterations of fractal pattern during diseased statuses. We developed a non-invasive visible optical heart rate recording system especially suitable for long-term recording by using principal component analysis (PCA) instead of fluorescence recording system to avoid the confounding effect from intense light irradiation...
2016: Scientific Reports
Kailey J Soller, Jing Yang, Gianluigi Veglia, Michael T Bowser
The sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) and phospholamban (PLN) complex regulate heart relaxation through its removal of cytosolic Ca2+ during diastole. Dysfunction of this complex has been related to many heart disorders and is therefore a key pharmacological target. There are currently no therapeutics that directly target either SERCA or PLN. It has been previously reported that single-stranded DNA binds PLN with strong affinity and relieves inhibition of SERCA in a length-dependent manner. In the current article we demonstrate that RNAs and single-stranded oligonucleotide analogs, or XNAs, also bind PLN strongly (Kd <10 nM) and relieve inhibition of SERCA...
August 16, 2016: Journal of Biological Chemistry
Alejandra Z Vielma, Luisa León, Ignacio C Fernández, Daniel R González, Mauricio P Boric
S-nitrosylation of several Ca2+ regulating proteins in response to β-adrenergic stimulation was recently described in the heart; however the specific nitric oxide synthase (NOS) isoform and signaling pathways responsible for this modification have not been elucidated. NOS-1 activity increases inotropism, therefore, we tested whether β-adrenergic stimulation induces NOS-1-dependent S-nitrosylation of total proteins, the ryanodine receptor (RyR2), SERCA2 and the L-Type Ca2+ channel (LTCC). In the isolated rat heart, isoproterenol (10 nM, 3-min) increased S-nitrosylation of total cardiac proteins (+46±14%) and RyR2 (+146±77%), without affecting S-nitrosylation of SERCA2 and LTCC...
2016: PloS One
Zai Hao Zhao, Chun Li Jin, Ji Hyun Jang, Yu Na Wu, Sung Joon Kim, Hong Hua Jin, Lan Cui, Yin Hua Zhang
Heart failure and cardiac arrhythmias are the leading causes of mortality and morbidity worldwide. However, the mechanism of pathogenesis and myocardial malfunction in the diseased heart remains to be fully clarified. Recent compelling evidence demonstrates that changes in the myofilament Ca(2+) sensitivity affect intracellular Ca(2+) homeostasis and ion channel activities in cardiac myocytes, the essential mechanisms responsible for the cardiac action potential and contraction in healthy and diseased hearts...
2016: Journal of Visualized Experiments: JoVE
Qiuping Chen, Tongda Xu, Dongye Li, Defeng Pan, Pei Wu, Yuanyuan Luo, Yanfeng Ma, Yang Liu
Recent studies have demonstrated that diabetes impairs the phosphatidylinositol 3-kinase/Akt (PI3K/Akt) pathway, while insulin resistance syndrome has been associated with alterations of this pathway in diabetic rats after ischemia/reperfusion (I/R), and activation of C-jun N-terminal kinase (JNK) is involved. The present study was designed to investigate whether inhibiting JNK activity would partially restore the PI3K/Akt signaling pathway and protect against myocardial I/R injury in diabetic rats, and to explore the effect of intervention with salvianolic acid A (Sal A)...
2016: American Journal of Translational Research
Sercan Okutucu, Mustafa Aparci, Cengiz Sabanoglu, Ugur Nadir Karakulak, Hakan Aksoy, Cengiz Ozturk, Mehmet Karaduman, Zafer Isilak, Adem Adar, Ali Oto
BACKGROUND: Heart rate (HR) recovery (HRR) reflects autonomic activity and predicts cardiovascular events. The aim of this study was to assess HRR in patients with myocardial bridge (MB). METHODS: Medical recordings of 93 patients with MB and appropriate age, compared to 78 sex-matched healthy subjects were analyzed. MB was diagnosed via coronary computed tomography angiography after a positive exercise stress test (EST). HRR indices were calculated by subtracting 1st (HRR1), 2nd (HRR2) and 3rd (HRR3) minute HR from the maximal HR during EST...
July 7, 2016: Cardiology Journal
Emre Oto, Sercan Okutucu, Deniz Katircioglu-Öztürk, Halil Altay Güvenir, Ergun Karaagaoglu, Martin Borggrefe, Günter Breithardt, Andreas Goette, Ursula Ravens, Gerhard Steinbeck, Karl Wegscheider, Ali Oto, Paulus Kirchhof
AIMS: Data mining is the computational process to obtain information from a data set and transform it for further use. Herein, through data mining with supportive statistical analyses, we identified and consolidated variables of the Flecainide Short-Long (Flec-SL-AFNET 3) trial dataset that are associated with the primary outcome of the trial, recurrence of persistent atrial fibrillation (AF) or death. METHODS AND RESULTS: The 'Ranking Instances by Maximizing the Area under the ROC Curve' (RIMARC) algorithm was applied to build a classifier that can predict the primary outcome by using variables in the Flec-SL dataset...
July 4, 2016: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
Sunil Jit R J Logantha, Mathis K Stokke, Andrew J Atkinson, Sanjay R Kharche, Sajida Parveen, Yawer Saeed, Ivar Sjaastad, Ole M Sejersted, Halina Dobrzynski
BACKGROUND: The sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2) pump is an important component of the Ca(2+)-clock pacemaker mechanism that provides robustness and flexibility to sinus node pacemaking. We have developed transgenic mice with reduced cardiac SERCA2 abundance (Serca2 KO) as a model for investigating SERCA2's role in sinus node pacemaking. METHODS AND RESULTS: In Serca2 KO mice, ventricular SERCA2a protein content measured by Western blotting was 75% (P < 0...
2016: Frontiers in Physiology
Agnieszka Łukasiak, Agata Skup, Stefan Chlopicki, Magdalena Łomnicka, Patrycja Kaczara, Bartosz Proniewski, Adam Szewczyk, Antoni Wrzosek
A large conductance potassium (BKCa) channel opener, NS1619 (1,3-dihydro-1- [2-hydroxy-5-(trifluoromethyl) phenyl]-5-(trifluoromethyl)-2H-benzimidazole-2-one), is well known for its protective effects against ischemia-reperfusion injury; however, the exact mode of its action remains unclear. The aim of this study was to characterize the effect of NS1619 on endothelial cells. The endothelial cell line EA.hy926, guinea pig hearts and submitochondrial particles isolated from the heart were used. In the isolated guinea pig hearts, which were perfused using the Langendorff technique, NS1619 caused a dose-dependent increase in coronary flow that was inhibited by L-NAME...
September 5, 2016: European Journal of Pharmacology
Yuanzhao L Darcy, Paula L Diaz-Sylvester, Julio A Copello
K201 (JTV-519) may prevent abnormal Ca(2+) leak from the sarcoplasmic reticulum (SR) in the ischemic heart and skeletal muscle (SkM) by stabilizing the ryanodine receptors (RyRs; RyR1 and RyR2, respectively). We tested direct modulation of the SR Ca(2+)-stimulated ATPase (SERCA) and RyRs by K201. In isolated cardiac and SkM SR microsomes, K201 slowed the rate of SR Ca(2+) loading, suggesting potential SERCA block and/or RyR agonism. K201 displayed Ca(2+)-dependent inhibition of SERCA-dependent ATPase activity, which was measured in microsomes incubated with 200, 2, and 0...
August 2016: Molecular Pharmacology
Daniel J Sassoon, Adam G Goodwill, Jillian N Noblet, Abass M Conteh, B Paul Herring, Jeanette N McClintick, Johnathan D Tune, Kieren J Mather
This study tested the hypothesis that obesity alters the cardiac response to ischemia/reperfusion and/or glucagon like peptide-1 (GLP-1) receptor activation, and that these differences are associated with alterations in the obese cardiac proteome and microRNA (miRNA) transcriptome. Ossabaw swine were fed normal chow or obesogenic diet for 6 months. Cardiac function was assessed at baseline, during a 30-minutes coronary occlusion, and during 2 hours of reperfusion in anesthetized swine treated with saline or exendin-4 for 24 hours...
July 2016: Basic Research in Cardiology
Morten A Høydal, Tomas O Stølen, Sarah Kettlewell, Lars S Maier, Joan Heller Brown, Tomas Sowa, Daniele Catalucci, Gianluigi Condorelli, Ole J Kemi, Godfrey L Smith, Ulrik Wisløff
Several conditions of heart disease, including heart failure and diabetic cardiomyopathy, are associated with upregulation of cytosolic Ca(2+)/calmodulin-dependent protein kinase II (CaMKIIδC) activity. In the heart, CaMKIIδC isoform targets several proteins involved in intracellular Ca(2+) homeostasis. We hypothesized that high-intensity endurance training activates mechanisms that enable a rescue of dysfunctional cardiomyocyte Ca(2+) handling and thereby ameliorate cardiac dysfunction despite continuous and chronic elevated levels of CaMKIIδC CaMKIIδC transgenic (TG) and wild-type (WT) mice performed aerobic interval exercise training over 6 wk...
July 1, 2016: Journal of Applied Physiology
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