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

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https://www.readbyqxmd.com/read/28800400/mechanism-of-tfam-mediated-cardiomyocyte-protection
#1
George H Kunkel, Pankaj Chaturvedi, Nicholas Theilen, Rohit Nair, Suresh C Tyagi
Although mitochondrial transcription factor A (TFAM) is a protective component of mitochondrial DNA and a regulator of calcium and reactive oxygen species (ROS) production, the mechanism remains unclear. In heart failure (HF), TFAM is significantly decreased and cardiomyocyte instability ensues. TFAM inhibits Nuclear Factor of Activated T cells (NFAT), which reduces ROS production; additionally, TFAM transcriptionally activates SERCA2a to decrease free calcium. Therefore, decreasing TFAM vastly increases protease expression and hypertrophic factors, leading to cardiomyocyte functional decline...
August 11, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28798077/cardiovascular-susceptibility-to-in-vivo-ischemic-myocardial-injury-in-male-and-female-rat-offspring-exposed-to-prenatal-hypoxia
#2
Amin Shah, Nobutoshi Matsumura, Anita Quon, Jude S Morton, Jason R B Dyck, Sandra T Davidge
Intrauterine growth restriction (IUGR) following prenatal hypoxia exposure leads to a higher risk of developing cardiovascular disease (CVD) in later life. Our aim was to evaluate cardiac susceptibility and its pathophysiological mechanisms following acute myocardial infarction (MI) in adult rat offspring exposed to prenatal hypoxia. Male and female rat offspring, which experienced normoxia (21% O2) or hypoxia (11% O2) in utero underwent sham or MI surgery at 12 weeks of age. Echocardiographic data revealed that both sexes had systolic dysfunction following MI surgery, independent of prenatal hypoxia...
September 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28795720/restoring-calcium-homeostasis-in-diabetic-cardiomyocytes-an-investigation-through-mathematical-modelling
#3
Phonindra Nath Das, Ajay Kumar, Nandadulal Bairagi, Samrat Chatterjee
Calcium homeostasis is a key factor in the regulation of cardiac excitation-contraction coupling. Calcium dynamics in cardiomyocytes is governed by ATP which depends on insulin dependent glucose concentration, via the glucose transporter type 4 (GLUT4) transporter. It would therefore be interesting to see how calcium dynamics changes in a cardiomyocyte under diabetic conditions. We proposed and analysed a four dimensional ordinary differential equation (ODE) model to capture the interdependency of calcium dynamics on glucose uptake and ATP generation...
August 10, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28767701/cardiac-directed-expression-of-a-catalytically-inactive-adenylyl-cyclase-6-protects-the-heart-from-sustained-%C3%AE-adrenergic-stimulation
#4
Mei Hua Gao, N Chin Lai, Dimosthenis Giamouridis, Young Chul Kim, Tracy Guo, H Kirk Hammond
OBJECTIVES: Increased expression of adenylyl cyclase type 6 (AC6) has beneficial effects on the heart through cyclic adenosine monophosphate (cAMP)-dependent and cAMP-independent pathways. We previously generated a catalytically inactive mutant of AC6 (AC6mut) that has an attenuated response to β-adrenergic receptor stimulation, and, consequently, exhibits reduced myocardial cAMP generation. In the current study we test the hypothesis that cardiac-directed expression of AC6mut would protect the heart from sustained β-adrenergic receptor stimulation, a condition frequently encountered in patients with heart failure...
2017: PloS One
https://www.readbyqxmd.com/read/28763488/anthocyanin-rich-extract-of-brassica-oleracea-l-alleviates-experimentally-induced-myocardial-infarction
#5
Sarmita Jana, Dipak Patel, Shweta Patel, Kapil Upadhyay, Jaymesh Thadani, Rahul Mandal, Santasabuj Das, Ranjitsinh Devkar
Cardioprotective potential of anthocyanin rich red cabbage extract (ARCE) was assessed in H2O2 treated rat neonatal cardiomyoblasts (H9c2 cells) and isoproterenol (ISO) induced rodent model of myocardial infarction. H2O2 treated H9c2 cells recorded cytotoxicity (48-50%) and apoptosis (57.3%), the same were reduced in presence of ARCE (7-10% & 12.3% respectively). Rats pretreated with ARCE for 30 days followed by ISO treatment recorded favourable heart: body weight ratio as compared to ISO treated group. Also, the mRNA levels of enzymatic antioxidants (sod and catalase) and apoptotic genes (bax and bcl-2) in ARCE+ISO treated group were similar to the control group suggesting that ARCE pretreatment prevents ISO induced depletion of enzymatic antioxidants and apoptosis...
2017: PloS One
https://www.readbyqxmd.com/read/28752958/increased-ca-buffering-underpins-remodelling-of-ca-2-handling-in-old-sheep-atrial-myocytes
#6
J D Clarke, J L Caldwell, C M Pearman, D A Eisner, A W Trafford, K M Dibb
Many cardiovascular diseases, including those affecting the atria, are associated with advancing age. Arrhythmias, including those in the atria, can arise due to electrical remodelling or alterations in Ca(2+) homeostasis. In the atria, age-associated changes in the action potential have been documented. However, little is known about remodelling of intracellular Ca(2+) homeostasis in the healthy aged heart. Using single atrial myocytes from young and aged Welsh Mountain sheep, we show the free Ca(2+) transient amplitude and rate of decay of systolic Ca(2+) decrease with age while sarcoplasmic reticulum (SR) Ca content increases...
July 28, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28750934/serca2a-a-potential-non-invasive-biomarker-of-cardiac-allograft-rejection
#7
Estefanía Tarazón, Ana Ortega, Carolina Gil-Cayuela, Elena Sánchez-Lacuesta, Pilar Marín, Francisca Lago, José Ramón González-Juanatey, Luis Martínez-Dolz, Manuel Portolés, Miguel Rivera, Esther Roselló-Lletí
BACKGROUND: The detection of heart transplant rejection by non-invasive methods remains a major challenge. Despite the well-known importance of the study of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) in the heart, its role as a rejection marker has never been analyzed. Our objective in this study was to determine whether circulating SERCA2a could be a good marker of cardiac rejection. METHODS: We collected 127 consecutive endomyocardial biopsies (EMBs) and serum samples from adult heart transplant recipients (49 without allograft rejection and 78 with the diagnosis of biopsy allograft rejection, including 48 Grade 1R, 21 Grade 2R and 9 Grade 3R)...
July 5, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28734932/a-pyridone-derivative-activates-serca2a-by-attenuating-the-inhibitory-effect-of-phospholamban
#8
Manami Kaneko, Hisato Yamamoto, Hiroki Sakai, Yusuke Kamada, Toshiki Tanaka, Shuji Fujiwara, Synsuke Yamamoto, Hiroki Takahagi, Hideyuki Igawa, Shizuo Kasai, Masakuni Noda, Makoto Inui, Tomoyuki Nishimoto
The cardiac sarco/endoplasmic reticulum Ca(2+)-dependent ATPase 2a (SERCA2a) plays a central role in Ca(2+) handling within cardiomyocytes and is negatively regulated by phospholamban (PLN), a sarcoplasmic reticulum (SR) membrane protein. The activation of SERCA2a, which has been reported to improve cardiac dysfunction in heart failure, is a potential therapeutic approach for heart failure. Therefore, we developed a novel small molecule, compound A and characterized it both in vitro and in vivo. Compound A activated the Ca(2+)-dependent ATPase activity of cardiac SR vesicles but not that of skeletal muscle SR vesicles that lack PLN...
July 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28728119/nf-%C3%AE%C2%BAb-mediated-inflammation-correlates-with-calcium-overload-under-arsenic-trioxide-induced-myocardial-damage-in-gallus-gallus
#9
Siwen Li, Yu Wang, Hongjing Zhao, Ying He, Jinglun Li, Guangshun Jiang, Mingwei Xing
Arsenic is a known environmental pollutant and highly hazardous toxin to human health. Due to the biological accumulation, arsenic produces a variety of cardiovascular diseases. However, the exact mechanism is still unclear. Here, our objective was to evaluate myocardial damage and determine the potential mechanism under arsenic exposure in chickens. Arsenic trioxide (As2O3) (1.25 mg/kg BW, corresponding 15 mg/kg feed) was administered as basal diet to male Hy-line chickens (one-day-old) for 4, 8 and 12 weeks...
October 2017: Chemosphere
https://www.readbyqxmd.com/read/28727756/dysregulation-of-micrornas-and-renin-angiotensin-system-in-high-salt-diet-induced-cardiac-dysfunction-in-uninephrectomized-rats
#10
Venkateswara Rao Amara, Sunil Kumar Surapaneni, Kulbhushan Tikoo
Uninephrectomy is not associated with major adverse events in cardiovascular and renal functions of live kidney donors. The effect of high salt diet on the quality of life of live kidney donors is largely unknown. Hence in this study, we aimed to determine the effect of high salt diet on the alterations of renin-angiotensin system and microRNAs leading to CV and renal dysfunction in uninephrectomized rats. In order to mimic clinical scenario, uninephrectomized male Sprague Dawley rats were fed initially with normal pellet diet for 12 weeks and then for 20 weeks with high salt (10% w/w NaCl) diet...
2017: PloS One
https://www.readbyqxmd.com/read/28724751/tomo-seq-identifies-sox9-as-a-key-regulator-of-cardiac-fibrosis-during-ischemic-injury
#11
Grégory P A Lacraz, Jan Philipp Junker, Monika M Gladka, Bas Molenaar, Koen T Scholman, Marta Vigil-Garcia, Danielle Versteeg, Hesther de Ruiter, Marit W Vermunt, Menno P Creyghton, Manon M H Huibers, Nicolaas de Jonge, Alexander van Oudenaarden, Eva van Rooij
Background -Cardiac ischemic injury induces a pathological remodeling response, which can ultimately lead to heart failure. Detailed mechanistic insights into molecular signaling pathways relevant for different aspects of cardiac remodeling will support the identification of novel therapeutic targets. Methods -While genome-wide transcriptome analysis on diseased tissues has greatly advanced our understanding of the regulatory networks that drive pathological changes in the heart, this approach has been disadvantaged by the fact that the signals are derived from tissue homogenates...
July 19, 2017: Circulation
https://www.readbyqxmd.com/read/28698769/high-intensity-exercise-reduces-cardiac-fibrosis-and-hypertrophy-but-does-not-restore-the-nitroso-redox-imbalance-in-diabetic-cardiomyopathy
#12
Ulises Novoa, Diego Arauna, Marisol Moran, Madelaine Nuñez, Sebastián Zagmutt, Sergio Saldivia, Cristian Valdes, Jorge Villaseñor, Carmen Gloria Zambrano, Daniel R Gonzalez
Diabetic cardiomyopathy refers to the manifestations in the heart as a result of altered glucose homeostasis, reflected as fibrosis, cellular hypertrophy, increased oxidative stress, and apoptosis, leading to ventricular dysfunction. Since physical exercise has been indicated as cardioprotective, we tested the hypothesis that high-intensity exercise training could reverse the cardiac maladaptations produced by diabetes. For this, diabetes was induced in rats by a single dose of alloxan. Diabetic rats were randomly assigned to a sedentary group or submitted to a program of exercise on a treadmill for 4 weeks at 80% of maximal performance...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28681509/akt2-ablation-prolongs-life-span-and-improves-myocardial-contractile-function-with-adaptive-cardiac-remodeling-role-of-sirt1-mediated-autophagy-regulation
#13
Jun Ren, Lifang Yang, Li Zhu, Xihui Xu, Asli F Ceylan, Wei Guo, Jian Yang, Yingmei Zhang
Aging is accompanied with unfavorable geometric and functional changes in the heart involving dysregulation of Akt and autophagy. This study examined the impact of Akt2 ablation on life span and cardiac aging as well as the mechanisms involved with a focus on autophagy and mitochondrial integrity. Cardiac geometry, contractile, and intracellular Ca(2+) properties were evaluated using echocardiography, IonOptix(®) edge-detection and fura-2 techniques. Levels of Sirt1, mitochondrial integrity, autophagy, and mitophagy markers were evaluated using Western blot...
July 5, 2017: Aging Cell
https://www.readbyqxmd.com/read/28670631/cardiac-directed-expression-of-adenylyl-cyclase-catalytic-domain-reverses-cardiac-dysfunction-caused-by-sustained-beta-adrenergic-receptor-stimulation
#14
Mei Hua Gao, N Chin Lai, Dimosthenis Giamouridis, Young Chul Kim, Zhen Tan, Tracy Guo, Wolfgang H Dillmann, Jorge Suarez, H Kirk Hammond
OBJECTIVE: To test the hypothesis that cardiac-directed expression of the cytoplasmic domains of adenylyl cyclase-6 (AC6) would have beneficial effects on the heart. BACKGROUND: Eliminating the two transmembrane domains of AC6 yields a protein with an intact catalytic domain that is disengaged from membrane-associated β-adrenergic receptor stimulation, but with enhanced propensity for intracellular interactions. METHODS: We constructed a peptide of the C1 and C2 segments of AC6 (C1C2), expressed C1C2 in an adenovirus vector and generated transgenic lines with cardiac-directed C1C2 expression, which underwent sustained isoproterenol (Iso) infusion...
December 2016: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/28649129/c33-s-a-novel-pde9a-inhibitor-protects-against-rat-cardiac-hypertrophy-through-upregulating-cgmp-signaling
#15
Pan-Xia Wang, Zhuo-Ming Li, Si-Dong Cai, Jing-Yan Li, Ping He, Yi Huang, Guo-Shuai Feng, Hai-Bin Luo, Shao-Rui Chen, Pei-Qing Liu
Phosphodiesterase-9A (PDE9A) expression is upregulated during cardiac hypertrophy and heart failure. Accumulating evidence suggests that PDE9A might be a promising therapeutic target for heart diseases. The present study sought to investigate the effects and underlying mechanisms of C33(S), a novel selective PDE9A inhibitor, on cardiac hypertrophy in vitro and in vivo. Treatment of neonatal rat cardiomyocytes (NRCMs) with PE (100 μmol/L) or ISO (1 μmol/L) induced cardiac hypertrophy characterized by significantly increased cell surface areas and increased expression of fetal genes (ANF and BNP)...
June 26, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28649039/pm2-5-exposure-in-utero-contributes-to-neonatal-cardiac-dysfunction-in-mice
#16
Vineeta Tanwar, Jeremy M Adelstein, Jacob A Grimmer, Dane J Youtz, Benjamin P Sugar, Loren E Wold
OBJECTIVE: Exposure of fine particulate matter (PM2.5) to pregnant dams has been shown to be strongly associated with adverse cardiovascular outcomes in offspring at adulthood, however, effects evident during neonatal periods are unclear. We designed this study to examine cardiac function of neonatal mice (14 days old) exposed to in utero PM2.5. METHODS: Pregnant FVB female mice were exposed either to filtered air (FA) or PM2.5 at an average concentration of 91...
June 22, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28643218/empagliflozin-improves-left-ventricular-diastolic-dysfunction-in-a-genetic-model-of-type-2-diabetes
#17
Nadjib Hammoudi, Dongtak Jeong, Rajvir Singh, Ahmed Farhat, Michel Komajda, Eric Mayoux, Roger Hajjar, Djamel Lebeche
PURPOSE: Cardiovascular (CV) diseases in type 2 diabetes (T2DM) represent an enormous burden with high mortality and morbidity. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have recently emerged as a new antidiabetic class that improves glucose control, as well as body weight and blood pressure with no increased risk of hypoglycemia. The first CV outcome study terminated with empagliflozin, a specific SGLT2 inhibitor, has shown a reduction in CV mortality and in heart failure hospitalization, suggesting a beneficial impact on cardiac function which remains to be demonstrated...
June 22, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28642329/experimental-and-computational-insight-into-human-mesenchymal-stem-cell-paracrine-signaling-and-heterocellular-coupling-effects-on-cardiac-contractility-and-arrhythmogenicity
#18
Joshua Mayourian, Timothy J Cashman, Delaine K Ceholski, Bryce V Johnson, David Sachs, Deepak A Kaji, Susmita Sahoo, Joshua M Hare, Roger J Hajjar, Eric A Sobie, Kevin D Costa
Rationale: Myocardial delivery of human mesenchymal stem cells (hMSCs) is an emerging therapy for treating the failing heart. However, the relative effects of hMSC-mediated heterocellular coupling (HC) and paracrine signaling (PS) on human cardiac contractility and arrhythmogenicity remain unresolved. Objective: To better understand hMSC PS and HC effects on human cardiac contractility and arrhythmogenicity by integrating experimental and computational approaches. Methods and Results: Extending our previous hMSC-cardiomyocyte HC computational model, we incorporated experimentally calibrated hMSC PS effects on cardiomyocyte L-type calcium channel/SERCA activity and cardiac tissue fibrosis...
June 22, 2017: Circulation Research
https://www.readbyqxmd.com/read/28630914/deregulated-ca-2-cycling-underlies-the-development-of-arrhythmia-and-heart-disease-due-to-mutant-obscurin
#19
Li-Yen R Hu, Maegen A Ackermann, Peter A Hecker, Benjamin L Prosser, Brendan King, Kelly A O'Connell, Alyssa Grogan, Logan C Meyer, Christopher E Berndsen, Nathan T Wright, W Jonathan Lederer, Aikaterini Kontrogianni-Konstantopoulos
Obscurins are cytoskeletal proteins with structural and regulatory roles encoded by OBSCN. Mutations in OBSCN are associated with the development of hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Specifically, the R4344Q mutation present in immunoglobulin domain 58 (Ig58) was the first to be linked with the development of HCM. To assess the effects of R4344Q in vivo, we generated the respective knock-in mouse model. Mutant obscurins are expressed and incorporated normally into sarcomeres...
June 2017: Science Advances
https://www.readbyqxmd.com/read/28617952/systolic-ca-2-i-regulates-diastolic-levels-in-rat-ventricular-myocytes
#20
Rajiv Sankaranarayanan, Kornél Kistamás, David J Greensmith, Luigi A Venetucci, David A Eisner
KEY POINTS: For the heart to function as a pump, intracellular calcium concentration ([Ca(2+) ]i ) must increase during systole to activate contraction and then fall, during diastole, to allow the myofilaments to relax and the heart to refill with blood. The present study investigates the control of diastolic [Ca(2+) ]i in rat ventricular myocytes. We show that diastolic [Ca(2+) ]i is increased by manoeuvres that decrease sarcoplasmic reticulum function. This is accompanied by a decrease of systolic [Ca(2+) ]i such that the time-averaged [Ca(2+) ]i remains constant...
August 15, 2017: Journal of Physiology
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