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Fabiana de Salvi Guimarães, Wilson Max Almeida Monteiro de Moraes, Luis Henrique Marchesi Bozi, Pâmela R Souza, Ednei Luiz Antonio, Danilo Sales Bocalini, Paulo José Ferreira Tucci, Daniel Araki Ribeiro, Patricia Chakur Brum, Alessandra Medeiros
Dexamethasone is a potent and widely used anti-inflammatory and immunosuppressive drug. However, recent evidences suggest that dexamethasone cause pathologic cardiac remodeling, which later impairs cardiac function. The mechanism behind the cardiotoxic effect of dexamethasone is elusive. The present study aimed to verify if dexamethasone-induced cardiotoxicity would be associated with changes in the cardiac net balance of calcium handling protein and calcineurin signaling pathway activation. Wistar rats (~400 g) were treated with dexamethasone (35 µg/g) in drinking water for 15 days...
October 19, 2016: Molecular and Cellular Biochemistry
Reza Ashrafi, Marianne Yon, Lucy Pickavance, Joseph Yanni Gerges, Gershan Davis, John Wilding, Kun Jian, Henggui Zhang, George Hart, Mark Boyett
Introduction. Obesity is increasingly common and is associated with an increased prevalence of cardiac arrhythmias. The aim of this study was to see whether in obesity there is proarrhythmic gene expression of ventricular ion channels and related molecules. Methods and Results. Rats were fed on a high-fat diet and compared to control rats on a normal diet (n = 8). After 8 weeks, rats on the high-fat diet showed significantly greater weight gain and higher adiposity. Left ventricle samples were removed at 8 weeks and mRNA expression of ion channels and other molecules was measured using qPCR...
2016: Journal of Obesity
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
Sophie Le Page, Marjorie Niro, Jérémy Fauconnier, Laura Cellier, Sophie Tamareille, Abdallah Gharib, Arnaud Chevrollier, Laurent Loufrani, Céline Grenier, Rima Kamel, Emmanuelle Sarzi, Alain Lacampagne, Michel Ovize, Daniel Henrion, Pascal Reynier, Guy Lenaers, Delphine Mirebeau-Prunier, Fabrice Prunier
BACKGROUND: Recent data suggests the involvement of mitochondrial dynamics in cardiac ischemia/reperfusion (I/R) injuries. Whilst excessive mitochondrial fission has been described as detrimental, the role of fusion proteins in this context remains uncertain. OBJECTIVES: To investigate whether Opa1 (protein involved in mitochondrial inner-membrane fusion) deficiency affects I/R injuries. METHODS AND RESULTS: We examined mice exhibiting Opa1delTTAG mutations (Opa1+/-), showing 70% Opa1 protein expression in the myocardium as compared to their wild-type (WT) littermates...
2016: PloS One
Adam S Helms, Francisco J Alvarado, Jaime Yob, Vi T Tang, Francis Pagani, Mark W Russell, Héctor H Valdivia, Sharlene M Day
BACKGROUND: -Aberrant calcium signaling may contribute to arrhythmias and adverse remodeling in hypertrophic cardiomyopathy (HCM). Mutations in sarcomere genes may distinctly alter calcium handling pathways. METHODS: -We analyzed gene expression, protein levels, and functional assays for calcium regulatory pathways in human HCM surgical samples with (n=25) and without (n=10) sarcomere mutations compared with control hearts (n=8). RESULTS: -Gene expression and protein levels for calsequestrin, L-type calcium channel, sodium-calcium exchanger, phospholamban (PLN), calcineurin, and calcium/calmodulin-dependent protein kinase type II (CaMKII) were similar in HCM compared to controls...
September 29, 2016: Circulation
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
Adonis Z Wu, Dongzhu Xu, Na Yang, Shien-Fong Lin, Peng-Sheng Chen, Steven E Cala, Zhenhui Chen
AIMS: Phospholamban (PLB) regulates the cardiac Ca(2+)-ATPase (SERCA2a) in sarcoplasmic reticulum (SR). However, the localization of PLB at subcellular sites outside the SR and possible contributions to Ca(2+) cycling remain unknown. We examined the intracellular distribution of PLB and tested whether a pool of PLB exists in the nuclear envelope (NE) that might regulate perinuclear/nuclear Ca(2+) (nCa(2+)) handling in cardiomyocytes (CMs). METHODS AND RESULTS: Using confocal immunofluorescence microscopy and immunoblot analyses of CMs and CM nuclei, we discovered that PLB was highly concentrated in NE...
September 15, 2016: Journal of Molecular and Cellular Cardiology
Yufen Li, Xiaomei Wang, Changli Lou
BACKGROUND Calcium overload, inflammation, and apoptosis play important roles in myocardial ischemia-reperfusion injury (MIRI). Gastrodin pretreatment can alleviate MIRI. This study observed sarcoplasmic reticulum calcium transport ATPase (Ca2+-ATPase, SERCA) and calcium phosphate (PLB) protein expression in the ventricular remodeling process after myocardial infarction to explore the effect of gastrodin pretreatment on MIRI. MATERIAL AND METHODS Healthy 7-week-old male SD rats were randomly divided into a sham group (A), a model group (B), and gastrodin pretreatment groups C, D, and E (100, 200, and 400 mg/kg, respectively) with 20 in each group...
September 19, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
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
Tao Bai, Xinyue Hu, Yang Zheng, Shudong Wang, Jian Kong, Lu Cai
The bacterial endotoxin lipopolysaccharide (LPS) is a main culprit responsible for cardiac dysfunction in sepsis. This study examined whether resveratrol could protect against LPS-induced cardiac dysfunction by improving the sarcoplasmic endoplasmic reticulum Ca(2+)-ATPase (SERCA2a) activity. Echocardiographic parameters, cardiomyocyte contractile and Ca(2+) transient properties, markers for cardiac inflammation, cell death, and oxidative stress, SERCA2a activity, and the ratios of phospholamban (PLB) monomer to oligomer were measured...
October 1, 2016: American Journal of Physiology. Heart and Circulatory Physiology
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
Adrian Szobi, Martin Lichy, Slavka Carnicka, Dezider Pancza, Pavel Svec, Tana Ravingerova, Adriana Adameov
BACKGROUND: It is known that statins possess beneficial cardioprotective effects irrespective of lipid-lowering action and that cardiac injury due ischemia/reperfusion is associated with Ca2+ dysregulation resulting in contractile dysfunction. OBJECTIVE: With this background, we tested a hypothesis that simvastatin influences signaling of Ca2+/calmodulin-dependent protein kinase IIδ (CaMKIIδ), a protein kinase regulating both Ca2+ homeostasis and thick filament function, and thereby might underlie the mitigation of ischemia/reperfusion (I/R)-induced cardiac dysfunction...
August 13, 2016: Current Pharmaceutical Design
Stacey Dineen Rodenbeck, Chad A Zarse, Mikaela L McKenney-Drake, Rebecca S Bruning, Michael Sturek, Neal X Chen, Sharon M Moe
BACKGROUND: Vascular smooth muscle cells (VSMCs) exhibit phenotypic plasticity, promoting vascular calcification and increasing cardiovascular risk. Changes in VSMC intracellular calcium ([Ca(2+)]i) are a major determinant of plasticity, but little is known about changes in [Ca(2+)]i in chronic kidney disease (CKD). We have previously demonstrated such plasticity in aortas from our rat model of CKD and therefore sought to examine changes in [Ca(2+)]i during CKD progression. MATERIALS AND METHODS: We examined freshly isolated VSMCs from aortas of normal rats, Cy/+ rats (CKD) with early and advanced CKD, and advanced CKD rats treated without and with 3% calcium gluconate (CKD + Ca(2+)) to lower parathyroid hormone (PTH) levels...
August 9, 2016: Nephrology, Dialysis, Transplantation
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
Mai Chen, Jiajia Xin, Baohui Liu, Liyang Luo, Jiayi Li, Wen Yin, Mingkai Li
BACKGROUND: The transient receptor potential vanilloid type 1 (TRPV1) is expressed in the cardiovascular system, and increased TRPV1 expression has been associated with cardiac hypertrophy. Nevertheless, the role of TRPV1 in the pathogenesis of cardiac hypertrophy and the underlying molecular mechanisms remain unclear. METHODS AND RESULTS: In cultured cardiomyocytes, activation of TRPV1 increased cell size and elevated expression of atrial natriuretic peptide mRNA and intracellular calcium level, which was reversed by TRPV1 antagonist capsazepine...
2016: Journal of the American Heart Association
Daniele M Guizoni, Silvio A Oliveira-Junior, Sefora L R Noor, Luana U Pagan, Paula F Martinez, Aline R R Lima, Mariana J Gomes, Ricardo L Damatto, Marcelo D M Cezar, Camila Bonomo, Leonardo A M Zornoff, Katashi Okoshi, Marina P Okoshi
BACKGROUND: Physical exercise attenuates myocardial infarction (MI)-induced cardiac remodeling. However, it is unsettled whether late exercise modulates post-infarction cardiac remodeling differentially according to infarct size. We investigated the effects of exercise started at late stage heart failure on cardiac remodeling in rats with moderate and large sized MI. METHODS: Three months after MI, rats were assigned into sedentary and exercise groups. Exercise rats underwent treadmill for three months...
October 15, 2016: International Journal of Cardiology
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
Ashley H Fong, Mónica Romero-López, Christopher M Heylman, Mark Keating, David Tran, Agua Sobrino, Anh Q Tran, Hiep H Pham, Cristhian Fimbres, Paul D Gershon, Elliot L Botvinick, Steven C George, Christopher C W Hughes
Pluripotent stem cell-derived cardiomyocytes (CMs) have great potential in the development of new therapies for cardiovascular disease. In particular, human induced pluripotent stem cells (iPSCs) may prove especially advantageous due to their pluripotency, their self-renewal potential, and their ability to create patient-specific cell lines. Unfortunately, pluripotent stem cell-derived CMs are immature, with characteristics more closely resembling fetal CMs than adult CMs, and this immaturity has limited their use in drug screening and cell-based therapies...
August 2016: Tissue Engineering. Part A
Junaid A B Zaman, Leanne Harling, Hutan Ashrafian, Ara Darzi, Nigel Gooderham, Thanos Athanasiou, Nicholas S Peters
BACKGROUND: Post-operative atrial fibrillation (POAF) is a major health economic burden. However, the precise mechanisms in POAF remain unclear. In other forms of AF, sites of high dominant frequency (DF) in sinus rhythm (SR) may harbour 'AF nests'. We studied AF inducibility in relation to substrate changes using epicardial electrograms and cardiomyocyte calcium handling in the atria of AF naïve patients. METHOD: Bipolar electrograms were recorded from the lateral right atrial (RA) wall in 34 patients undergoing coronary surgery using a high-density array in sinus rhythm (NSR)...
October 1, 2016: International Journal of Cardiology
A Mark Evans, Nicola Fameli, Oluseye A Ogunbayo, Jingxian Duan, Jorge Navarro-Dorado
Calcium signals determine, for example, smooth muscle contraction and changes in gene expression. How calcium signals select for these processes is enigmatic. We build on the "panjunctional sarcoplasmic reticulum" hypothesis, describing our view that different calcium pumps and release channels, with different kinetics and affinities for calcium, are strategically positioned within nanojunctions of the SR and help demarcate their respective cytoplasmic nanodomains. SERCA2b and RyR1 are preferentially targeted to the sarcoplasmic reticulum (SR) proximal to the plasma membrane (PM), i...
August 2016: Science China. Life Sciences
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