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SERCA2a

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https://www.readbyqxmd.com/read/28734932/a-pyridone-derivative-activates-serca2a-by-attenuating-the-inhibitory-effect-of-phospholamban
#1
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/28681509/akt2-ablation-prolongs-life-span-and-improves-myocardial-contractile-function-with-adaptive-cardiac-remodeling-role-of-sirt1-mediated-autophagy-regulation
#2
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
#3
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/28665545/inhibition-of-mevalonate-pathway-prevents-ischemia-induced-cardiac-dysfunction-in-rats-via-rhoa-independent-signaling-pathway
#4
Ying Yang, Xiqing Rong, Xue Lv, Wenbing Jiang, Yuan Yang, Dongwu Lai, Shiming Xu, Guosheng Fu
AIM: We previously demonstrated that anoxia-mediated Ca(2+) handling dysfunction could be ameliorated through inhibition of mevalonate pathway via RhoA- and Ras-related mechanisms in H9c2 cells. In this study, we further explored whether inhibition of mevalonate pathway is associated with cardiac remodeling and dysfunction in ischemic cardiomyopathy, and discuss the possible role of Ras, Rac and RhoA in cardiac dysfunction. METHODS: We investigated the role of mevalonate pathway in cardiac remodeling and cardiomyocyte Ca(2+) handling proteins expression in a rat model of cardiac dysfunction due to myocardial infarction (MI)...
June 30, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28656205/role-of-pka-in-the-process-of-neonatal-cardiomyocyte-hypertrophy-induced-by-urotensin%C3%A2-ii
#5
Jianrong Xu, Qinghua Han, Hongtao Shi, Wenyuan Liu, Tingting Chu, Hao Li
The model of urotensin II (UII)-induced cardiomyocyte hypertrophy has been widely used in studies on hypertrophy. However, the molecular mechanisms responsible for UII-induced cardiomyocyte hypertrophy have not yet been fully elucidated. It has been demonstrated that cardiomyocyte hypertrophy induced by UII is associated with changes in the intracellular Ca2+ concentration. In the present study, we investigated whether the cAMP-dependent protein kinase A (PKA)‑mediated upregulation of the phosphorylation levels of phospholamban (PLN) at Ser16 contributes to UII-induced cardiomyocyte hypertrophy...
June 22, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28649129/c33-s-a-novel-pde9a-inhibitor-protects-against-rat-cardiac-hypertrophy-through-upregulating-cgmp-signaling
#6
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/28648117/alteration-of-sarcoplasmic-reticulum-ca-2-atpase-expression-in-lower-limb-ischemia-caused-by-atherosclerosis-obliterans
#7
J Fodor, A Gomba-Tóth, T Oláh, E Zádor, Zs Cs Tóth, I Ioannis, B Molnár, I Kovács, L Csernoch
Atherosclerosis is a disease caused by a build-up of fatty plaques and cholesterol in the arteries. The lumen of the vessels is obliterated resulting in restricted blood supply to tissues. In ischemic conditions, the cytosolic Ca(2+) level of skeletal muscle may increase, indicating the alteration of Ca(2+) removal mechanisms. Ca(2+) is transported from cytosol into the sarcoplasmic reticulum by Ca(2+) ATPase (SERCA), with its 1a isoform expressed in adult, while its 1b isoform in neonatal and regenerating fast-twitch skeletal muscle...
June 26, 2017: Physiology International
https://www.readbyqxmd.com/read/28643218/empagliflozin-improves-left-ventricular-diastolic-dysfunction-in-a-genetic-model-of-type-2-diabetes
#8
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
#9
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/28637456/the-modified-yi-qi-decoction-protects-cardiac-ischemia-reperfusion-induced-injury-in-rats
#10
Xiao Yu, Xiao-Dong Zhao, Rong-Qi Bao, Jia-Yu Yu, Guo-Xing Zhang, Jing-Wei Chen
BACKGROUND: To investigate the effects and involved mechanisms of the modified Yi Qi decoction (MYQ) in cardiac ischemia-reperfusion (IR) induced injury. METHODS: Male Sprague-Dawley rats were subjected to a 30-min coronary arterial occlusion followed by reperfusion, low or high dose decoction of MYQ was administrated orally for 1 week or 1 month. RESULTS: Both in 1 week and 1 month IR rat groups, cardiac function indexes were significantly impaired compared with sham group rats, accompanied with higher ratio of infarct size to risk size, decreased expressions of sodium calcium exchanger (NCX1) and sarcoplasmic reticulum Ca(2+)-ATPase (Serca2a), and different expressions of autophagic proteins, Beclin-1 and LC3...
June 21, 2017: BMC Complementary and Alternative Medicine
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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