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Journal of Molecular and Cellular Cardiology

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https://www.readbyqxmd.com/read/28529049/heterogeneity-of-transverse-axial-tubule-system-in-mouse-atria-remodeling-in-atrial-specific-na-ca-2-exchanger-knockout-mice
#1
Xin Yue, Rui Zhang, Brian Kim, Aiqun Ma, Kenneth D Philipson, Joshua I Goldhaber
Transverse-axial tubules (TATs) are commonly assumed to be sparse or absent in atrial myocytes from small animals. Atrial myocytes from rats, cats and rabbits lack TATs, which results in a characteristic "V"-shaped Ca release pattern in confocal line-scan recordings due to the delayed rise of Ca in the center of the cell. To examine TAT expression in isolated mouse atrial myocytes, we loaded them with the membrane dye Di-4-ANEPPS to label TATs. We found that >80% of atrial myocytes had identifiable TATs...
May 18, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28526246/impaired-mitophagy-facilitates-mitochondrial-damage-in-danon-disease
#2
Sherin I Hashem, Anne N Murphy, Ajit S Divakaruni, Matthew L Klos, Bradley C Nelson, Emily C Gault, Teisha J Rowland, Cynthia N Perry, Yusu Gu, Nancy D Dalton, William H Bradford, Eric J Devaney, Kirk L Peterson, Kenneth L Jones, Matthew R G Taylor, Ju Chen, Neil C Chi, Eric D Adler
RATIONALE: Lysosomal associated membrane protein type-2 (LAMP-2) is a highly conserved, ubiquitous protein that is critical for autophagic flux. Loss of function mutations in the LAMP-2 gene cause Danon disease, a rare X-linked disorder characterized by developmental delay, skeletal muscle weakness, and severe cardiomyopathy. We previously found that human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from Danon patients exhibited significant mitochondrial oxidative stress and apoptosis...
May 16, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28502796/in-vivo-reprogramming-for-heart-regeneration-a-glance-at-efficiency-environmental-impacts-challenges-and-future-directions
#3
REVIEW
Behnam Ebrahimi
Replacing dying or diseased cells of a tissue with new ones that are converted from patient's own cells is an attractive strategy in regenerative medicine. In vivo reprogramming is a novel strategy that can circumvent the hurdles of autologous/allogeneic cell injection therapies. Interestingly, studies have demonstrated that direct injection of cardiac transcription factors or specific miRNAs into the infarct border zone of murine hearts following myocardial infarction converts resident cardiac fibroblasts into functional cardiomyocytes...
May 11, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28502795/multi-scale-tailor-made-heart-simulation-can-predict-the-effect-of-cardiac-resynchronization-therapy
#4
Jun-Ichi Okada, Takumi Washio, Machiko Nakagawa, Masahiro Watanabe, Yoshimasa Kadooka, Taro Kariya, Hiroshi Yamashita, Yoko Yamada, Shin-Ichi Momomura, Ryozo Nagai, Toshiaki Hisada, Seiryo Sugiura
BACKGROUND: The currently proposed criteria for identifying patients who would benefit from cardiac resynchronization therapy (CRT) still need to be optimized. A multi-scale heart simulation capable of reproducing the electrophysiology and mechanics of a beating heart may help resolve this problem. The objective of this retrospective study was to test the capability of patient-specific simulation models to reproduce the response to CRT by applying the latest multi-scale heart simulation technology...
May 11, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28483598/the-mechano-sensitivity-of-cardiac-atp-sensitive-potassium-channels-is-mediated-by-intrinsic-mgatpase-activity
#5
Mohammad Fatehi, Christian C Carter, Nermeen Youssef, Peter E Light
Cardiac ATP-sensitive K(+) (KATP) channel activity plays an important cardio-protective role in regulating excitability in response to metabolic stress. Evidence suggests that these channels are also mechano-sensitive and therefore may couple KATP channel activity to increased cardiac workloads. However, the molecular mechanism that couples membrane stretch to channel activity is not currently known. We hypothesized that membrane stretch may alter the intrinsic MgATPase activity of the cardiac KATP channel resulting in increased channel activation...
May 5, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28483597/sub-microscopic-analysis-of-t-tubule-geometry-in-living-cardiac-ventricular-myocytes-using-a-shape-based-analysis-method
#6
Cherrie H T Kong, Eva A Rog-Zielinska, Clive H Orchard, Peter Kohl, Mark B Cannell
Transverse-axial tubules (TTs) are key structures involved in cardiac excitation-contraction coupling and can become deranged in disease. Although optical measurement of TTs is frequently employed to assess TT abundance and regularity, TT dimensions are generally below the diffraction limit of optical microscopy so determination of tubule size is problematic. TT diameter was measured by labeling both local surface membrane area and volume with fluorescent probes (FM4-64 and calcein, respectively), correcting image asymmetry by image processing and using the relationship between surface area and volume for a geometric primitive...
May 5, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28478048/regulation-of-cardiac-gap-junctions-by-protein-phosphatases
#7
REVIEW
Ashleigh R Hood, Xun Ai, Steven M Pogwizd
Sufficient connexin-mediated intercellular coupling is critical to maintain gap junctional communication for proper cardiac function. Alterations in connexin phosphorylation state, particularly dephosphorylation of connexin 43 (Cx43), may impact cell coupling and conduction in disease states. Cx43 dephosphorylation may be carried out by protein phosphatase activity. Here, we present an overview of the key phosphatases known to interact with Cx43 or modulators of Cx43, as well as some possible therapeutic targets to regulate phosphatase activity in the heart...
May 3, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28478047/plasma-metabolite-profiles-cellular-cholesterol-efflux-and-non-traditional-cardiovascular-risk-in-patients-with-ckd
#8
Anjali Ganda, Laurent Yvan-Charvet, Yuan Zhang, Eric J Lai, Renu Regunathan-Shenk, Farah N Hussain, Rupali Avasare, Bibhas Chakraborty, Annie J Febus, Linda Vernocchi, Rafael Lantigua, Ying Wang, Xu Shi, Joanne Hsieh, Andrew J Murphy, Nan Wang, Nora Bijl, Kristie M Gordon, Maria Hamm de Miguel, Jessica R Singer, Jonathan Hogan, Serge Cremers, Martin Magnusson, Olle Melander, Robert E Gerszten, Alan R Tall
BACKGROUND: Patients with chronic kidney disease (CKD) experience high rates of atherosclerotic cardiovascular disease and death that are not fully explained by traditional risk factors. In animal studies, defective cellular cholesterol efflux pathways which are mediated by the ATP binding cassette transporters ABCA1 and ABCG1 are associated with accelerated atherosclerosis. We hypothesized that cholesterol efflux in humans would vary in terms of cellular components, with potential implications for cardiovascular disease...
May 3, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28476659/effect-of-exercise-on-passive-myocardial-stiffness-in-mice-with-diastolic-dysfunction
#9
Rebecca E Slater, Joshua G Strom, Henk Granzier
Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome, characterized by increased diastolic stiffness and a preserved ejection fraction, with no effective treatment options. Here we studied the therapeutic potential of exercise for improving diastolic function in a mouse model with HFpEF-like symptoms, the TtnΔIAjxn mouse model. TtnΔIAjxn mice have increased diastolic stiffness and reduced exercise tolerance, mimicking aspects of HFpEF observed in patients. We investigated the effect of free-wheel running exercise on diastolic function...
May 3, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28476660/%C3%AE-adrenergic-induced-sr-ca-2-leak-is-mediated-by-an-epac-nos-pathway
#10
Laëtitia Pereira, Dan J Bare, Samuel Galice, Thomas R Shannon, Donald M Bers
Cardiac β-adrenergic receptors (β-AR) and Ca(2+)-Calmodulin dependent protein kinase (CaMKII) regulate both physiological and pathophysiological Ca(2+) signaling. Elevated diastolic Ca(2+) leak from the sarcoplasmic reticulum (SR) contributes to contractile dysfunction in heart failure and to arrhythmogenesis. β-AR activation is known to increase SR Ca(2+) leak via CaMKII-dependent phosphorylation of the ryanodine receptor. Two independent and reportedly parallel pathways have been implicated in this β-AR-CaMKII cascade, one involving exchange protein directly activated by cAMP (Epac2) and another involving nitric oxide synthase 1 (NOS1)...
May 2, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28457941/non-nuclear-estrogen-receptor-alpha-activation-in-endothelium-reduces-cardiac-ischemia-reperfusion-injury-in-mice
#11
Sara Menazza, Junhui Sun, Swathi Appachi, Ken L Chambliss, Sung Hoon Kim, Angel Aponte, Sohaib Khan, John A Katzenellenbogen, Benita S Katzenellenbogen, Philip W Shaul, Elizabeth Murphy
Steroid hormone receptors including estrogen receptors (ER) classically function as ligand-regulated transcription factors. However, estrogens also elicit cellular effects through binding to extra-nuclear ER (ERα, ERβ, and G protein-coupled ER or GPER) that are coupled to kinases. How extra-nuclear ER actions impact cardiac ischemia-reperfusion (I/R) injury is unknown. We treated ovariectomized wild-type female mice with estradiol or an estrogen-dendrimer conjugate (EDC), which selectively activates extra-nuclear ER, or vehicle interventions for two weeks...
April 27, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28431892/a-humanized-hla-dr4-mouse-model-for-autoimmune-myocarditis
#12
M Emrah Şelli, Anita C Thomas, David C Wraith, Andrew C Newby
Myocarditis, the principal cause of dilated cardiomyopathy and heart failure in young adults, is associated with autoimmunity to human cardiac α-myosin (hCAM) and the DR4 allele of human major histocompatibility II (MHCII). We developed an hCAM-induced myocarditis model in human HLA-DR4 transgenic mice that lack all mouse MHCII genes, demonstrating that immunization for 3weeks significantly increased splenic T-cell proliferative responses and titres of IgG1 and IgG2c antibodies, abolished weight gain, provoked cardiac inflammation and significantly impaired cardiac output and fractional shortening, by echocardiography, compared to adjuvant-injected mice...
April 18, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28427997/distinct-sequences-and-post-translational-modifications-in-cardiac-atrial-and-ventricular-myosin-light-chains-revealed-by-top-down-mass-spectrometry
#13
Zachery R Gregorich, Wenxuan Cai, Ziqing Lin, Albert J Chen, Ying Peng, Takushi Kohmoto, Ying Ge
Myosin is the principal component of the thick filaments that, through interactions with the actin thin filaments, mediates force production during muscle contraction. Myosin is a hexamer, consisting of two heavy chains, each associated with an essential (ELC) and a regulatory (RLC) light chain, which bind the lever-arm of the heavy chain and play important modulatory roles in striated muscle contraction. Nevertheless, a comprehensive assessment of the sequences of the ELC and RLC isoforms, as well as their post-translational modifications, in the heart remains lacking...
April 17, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28395930/acetylcholine-attenuated-tnf-%C3%AE-induced-intracellular-ca-2-overload-by-inhibiting-the-formation-of-the-ncx1-trpc3-ip3r1-complex-in-human-umbilical-vein-endothelial-cells
#14
Ming Zhao, Hang-Huan Jia, Long-Zhu Liu, Xue-Yuan Bi, Man Xu, Xiao-Jiang Yu, Xi He, Wei-Jin Zang
The endoplasmic reticulum (ER) forms discrete junctions with the plasma membrane (PM) that play a critical role in the regulation of Ca(2+) signaling during cellular bioenergetics, apoptosis and autophagy. We have previously confirmed that acetylcholine can inhibit ER stress and apoptosis after inflammatory injury. However, limited research has focused on the effects of acetylcholine on ER-PM junctions. In this work, we evaluated the structure and function of the supramolecular sodium-calcium exchanger 1 (NCX1)-transient receptor potential canonical 3 (TRPC3)-inositol 1,4,5-trisphosphate receptor 1 (IP3R1) complex, which is involved in regulating Ca(2+) homeostasis during inflammatory injury...
April 7, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28392437/a-model-of-cardiac-contraction-based-on-novel-measurements-of-tension-development-in-human-cardiomyocytes
#15
Sander Land, So-Jin Park-Holohan, Nicolas P Smith, Cristobal G Dos Remedios, Jonathan C Kentish, Steven A Niederer
Experimental data from human cardiac myocytes at body temperature is crucial for a quantitative understanding of clinically relevant cardiac function and development of whole-organ computational models. However, such experimental data is currently very limited. Specifically, important measurements to characterize changes in tension development in human cardiomyocytes that occur with perturbations in cell length are not available. To address this deficiency, in this study we present an experimental data set collected from skinned human cardiac myocytes, including the passive and viscoelastic properties of isolated myocytes, the steady-state force calcium relationship at different sarcomere lengths, and changes in tension following a rapid increase or decrease in length, and after constant velocity shortening...
April 7, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28365422/mechanisms-of-the-cyclic-nucleotide-cross-talk-signaling-network-in-cardiac-l-type-calcium-channel-regulation
#16
Claire Y Zhao, Joseph L Greenstein, Raimond L Winslow
Regulation of L-type Calcium (Ca(2+)) Channel (LCC) gating is critical to shaping the cardiac action potential (AP) and triggering the initiation of excitation-contraction (EC) coupling in cardiac myocytes. The cyclic nucleotide (cN) cross-talk signaling network, which encompasses the β-adrenergic and the Nitric Oxide (NO)/cGMP/Protein Kinase G (PKG) pathways and their interaction (cross-talk) through distinctively-regulated phosphodiesterase isoenzymes (PDEs), regulates LCC current via Protein Kinase A- (PKA) and PKG-mediated phosphorylation...
March 29, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28359939/tropomyosin-1-multiple-roles-in-the-developing-heart-and-in-the-formation-of-congenital-heart-defects
#17
Jennifer England, Javier Granados-Riveron, Luis Polo-Parada, Diji Kuriakose, Christopher Moore, J David Brook, Catrin S Rutland, Kerry Setchfield, Christopher Gell, Tushar K Ghosh, Frances Bu'Lock, Christopher Thornborough, Elisabeth Ehler, Siobhan Loughna
Tropomyosin 1 (TPM1) is an essential sarcomeric component, stabilising the thin filament and facilitating actin's interaction with myosin. A number of sarcomeric proteins, such as alpha myosin heavy chain, play crucial roles in cardiac development. Mutations in these genes have been linked to congenital heart defects (CHDs), occurring in approximately 1 in 145 live births. To date, TPM1 has not been associated with isolated CHDs. Analysis of 380 CHD cases revealed three novel mutations in the TPM1 gene; IVS1+2T>C, I130V, S229F and a polyadenylation signal site variant GATAAA/AATAAA...
March 27, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28342976/translating-the-microrna-signature-of-microvesicles-derived-from-human-coronary-artery-smooth-muscle-cells-in-patients-with-familial-hypercholesterolemia-and-coronary-artery-disease
#18
David de Gonzalo-Calvo, Ana Cenarro, Katia Garlaschelli, Fabio Pellegatta, David Vilades, Laura Nasarre, Sandra Camino-Lopez, Javier Crespo, Francesc Carreras, Rubén Leta, Alberico Luigi Catapano, Giuseppe Danilo Norata, Fernando Civeira, Vicenta Llorente-Cortes
AIMS: To analyze the impact of atherogenic lipoproteins on the miRNA signature of microvesicles derived from human coronary artery smooth muscle cells (CASMC) and to translate these results to familial hypercholesterolemia (FH) and coronary artery disease (CAD) patients. METHODS: Conditioned media was collected after exposure of CASMC to atherogenic lipoproteins. Plasma samples were collected from two independent populations of diagnosed FH patients and matched normocholesterolemic controls (Study population 1, N=50; Study population 2, N=24) and a population of patients with suspected CAD (Study population 3, N=50)...
March 23, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28322869/scaffold-free-high-throughput-generation-of-quiescent-valvular-microtissues
#19
Annelies Roosens, Inès Puype, Ria Cornelissen
AIMS: The major challenge of working with valvular interstitial cells in vitro is the preservation or recovery of their native quiescent state. In this study, a biomimetic approach is used which aims to engineer small volume, high quality valve microtissues, having a potential in regenerative medicine and as a relevant 3D in vitro model to provide insights into valve (patho)biology. METHODS AND RESULTS: To form micro-aggregates, porcine valvular interstitial cells were seeded in agarose micro-wells and cultured in medium supplemented with 250μM Ascorbic Acid 2-phosphate for 22days...
March 18, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28279663/mir-146a-mediates-inflammatory-changes-and-fibrosis-in-the-heart-in-diabetes
#20
Biao Feng, Shali Chen, Andrew Devon Gordon, Subrata Chakrabarti
Hyperglycemia induced endothelial injury is a key pathogenetic factor in diabetic cardiomyopathy. In diabetes, changes in pro-inflammatory cytokines are a key mechanism leading to cardiac fibrosis. We have previously demonstrated alteration of miR-146a in chronic diabetic complications. Here, we investigated the role of endothelial miR-146a in mediating inflammation and fibrosis in diabetic cardiomyopathy. To examine the effects of miR-146a on the inflammatory mediators, an endothelial specific miR-146a overexpressing transgenic mice (TG) using tie-2 promoter, was generated...
March 6, 2017: Journal of Molecular and Cellular Cardiology
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