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Journal of Molecular and Cellular Cardiology

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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
#1
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
#2
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
#3
Sander Land, So-Jin 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 6, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28366738/the-heartbreak-of-depression-psycho-cardiac-coupling-in-myocardial-infarction
#4
REVIEW
John P Headrick, Jason N Peart, Boris P Budiono, David H K Shum, David L Neumann, Nicolas J C Stapelberg
Ample evidence identifies strong links between major depressive disorder (MDD) and both risk of ischemic or coronary heart disease (CHD) and resultant morbidity and mortality. The molecular mechanistic bases of these linkages are poorly defined. Systemic factors linked to MDD, including vascular dysfunction, atherosclerosis, obesity and diabetes, together with associated behavioral changes, all elevate CHD risk. Nonetheless, experimental evidence indicates the myocardium is also directly modified in depression, independently of these factors, impairing infarct tolerance and cardioprotection...
March 31, 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
#5
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
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/28263756/neuregulin-1%C3%AE-induces-proliferation-survival-and-paracrine-signaling-in-normal-human-cardiac-ventricular-fibroblasts
#10
Annet Kirabo, Sergey Ryzhov, Manisha Gupte, Seng Sengsayadeth, Richard J Gumina, Douglas B Sawyer, Cristi L Galindo
Neuregulin-1β (NRG-1β) is critical for cardiac development and repair, and recombinant forms are currently being assessed as possible therapeutics for systolic heart failure. We previously demonstrated that recombinant NRG-1β reduces cardiac fibrosis in an animal model of cardiac remodeling and heart failure, suggesting that there may be direct effects on cardiac fibroblasts. Here we show that NRG-1β receptors (ErbB2, ErbB3, and ErbB4) are expressed in normal human cardiac ventricular (NHCV) fibroblast cell lines...
March 3, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28223222/disrupting-the-key-circadian-regulator-clock-leads-to-age-dependent-cardiovascular-disease
#11
Faisal J Alibhai, Jonathan LaMarre, Cristine J Reitz, Elena V Tsimakouridze, Jeffrey T Kroetsch, Steffen-Sebastian Bolz, Alex Shulman, Samantha Steinberg, Thomas P Burris, Gavin Y Oudit, Tami A Martino
The circadian mechanism underlies daily rhythms in cardiovascular physiology and rhythm disruption is a major risk factor for heart disease and worse outcomes. However, the role of circadian rhythms is generally clinically unappreciated. Clock is a core component of the circadian mechanism and here we examine the role of Clock as a vital determinant of cardiac physiology and pathophysiology in aging. Clock(Δ19/Δ19) mice develop age-dependent increases in heart weight, hypertrophy, dilation, impaired contractility, and reduced myogenic responsiveness...
February 20, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28223221/the-atheroma-plaque-secretome-stimulates-the-mobilization-of-endothelial-progenitor-cells-ex-vivo
#12
Francisco M Vega, Violette Gautier, Cecilia M Fernandez-Ponce, M J Extremera, A F M Altelaar, Jaime Millan, Juan C Tellez, Jose A Hernandez-Campos, Rosario Conejero, Jorge Bolivar, Ricardo Pardal, Francisco J Garcia-Cózar, Enrique Aguado, Albert J R Heck, Mª Carmen Duran-Ruiz
Endothelial progenitor cells (EPCs) constitute a promising alternative in cardiovascular regenerative medicine due to their assigned role in angiogenesis and vascular repair. In response to injury, EPCs promote vascular remodeling by replacement of damaged endothelial cells and/or by secreting angiogenic factors over the damaged tissue. Nevertheless, such mechanisms need to be further characterized. In the current approach we have evaluated the initial response of early EPCs (eEPCs) from healthy individuals after direct contact with the factors released by carotid arteries complicated with atherosclerotic plaques (AP), in order to understand the mechanisms underlying the neovascularization and remodeling properties assigned to these cells...
February 20, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28214509/haplodeficiency-of-activin-receptor-like-kinase-4-alleviates-myocardial-infarction-induced-cardiac-fibrosis-and-preserves-cardiac-function
#13
Yi-He Chen, Qian Wang, Chang-Yi Li, Jian-Wen Hou, Xiao-Meng Chen, Qing Zhou, Jie Chen, Yue-Peng Wang, Yi-Gang Li
Cardiac fibrosis (CF), a repairing process following myocardial infarction (MI), is characterized by abnormal proliferation of cardiac fibroblasts and excessive deposition of extracellular matrix (ECM) resulting in inevitable resultant heart failure. TGF-β (transforming growth factor-β)/ALK5 (Activin receptor-like kinase 5)/Smad2/3/4 pathways have been reported to be involved in the process. Recent studies have implicated both activin and its specific downstream component ALK4 in stimulating fibrosis in non-cardiac organs...
February 16, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28189650/functional-studies-can-contribute-to-predict-the-pathogenicity-of-a-novel-mutation-for-cardiomyopathy
#14
LETTER
Andreas Brodehl, Hendrik Milting
No abstract text is available yet for this article.
February 8, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28143713/intercellular-transfer-of-mir-126-3p-by-endothelial-microparticles-reduces-vascular-smooth-muscle-cell-proliferation-and-limits-neointima-formation-by-inhibiting-lrp6
#15
Felix Jansen, Tobias Stumpf, Sebastian Proebsting, Bernardo S Franklin, Daniela Wenzel, Philipp Pfeifer, Anna Flender, Theresa Schmitz, Xiaoyan Yang, Bernd K Fleischmann, Georg Nickenig, Nikos Werner
BACKGROUND: Vascular smooth muscle cell (VSMC) proliferation is of importance in the pathogenesis of vascular diseases such as restenosis or atherosclerosis. Endothelial microparticles (EMPs) regulate function and phenotype of target endothelial cells (ECs), but their influence on VSMC biology is unknown. We aim to investigate the role of EMPs in the regulation of vascular smooth muscle cell (VSMC) proliferation and vascular remodeling. METHODS AND RESULTS: Systemic treatment of mice with EMPs after vascular injury reduced neointima formation in vivo...
January 28, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28130118/targeting-the-pathway-of-gsk-3%C3%AE-nerve-growth-factor-to-attenuate-post-infarction-arrhythmias-by-preconditioned-adipose-derived-stem-cells
#16
Tsung-Ming Lee, Horng-Jyh Harn, Tzyy-Wen Chiou, Ming-Hsi Chuang, Chun-Hung Chen, Po-Cheng Lin, Shinn-Zong Lin
Adipose-derived stem cell (ADSC) transplantation is a promising new therapy to improve cardiac function after myocardial infarction. However, its low efficacy of transdifferentiation hampers its usefulness. Glycogen synthase kinase-3β (GSK-3β) signal has been shown to play a role in preconditioning-induced cardioprotection. We assessed whether n-butylidenephthalide (BP) primed ADSCs can attenuate arrhythmias by a GSK-3β-dependent pathway after myocardial infarction. Male Wistar rats after coronary ligation was randomly allocated to receive intramyocardial injection of vehicle, ADSCs, BP-preconditioned ADSCs, (BP+lithium)-preconditioned ADSCs, (BP+SB216763)-preconditioned ADSCs, and (BP+LY294002)-preconditioned ADSCs...
January 24, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28302382/congenital-heart-defect-causing-mutation-in-nkx2-5-displays-in-vivo-functional-deficit
#17
Abeer F Zakariyah, Rashida F Rajgara, John P Veinot, Ilona S Skerjanc, Patrick G Burgon
The Nkx2.5 gene encodes a transcription factor that plays a critical role in heart development. In humans, heterozygous mutations in NKX2.5 result in congenital heart defects (CHDs). However, the molecular mechanisms by which these mutations cause the disease remain unknown. NKX2.5-R142C is a mutation that was reported to be associated with atrial septal defect (ASD) and atrioventricular (AV) block in 13-patients from one family. The R142C mutation is located within both the DNA-binding domain and the nuclear localization sequence of NKX2...
April 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28274624/the-apolipoprotein-a-i-mimetic-peptide-d-4f-alleviates-ox-ldl-induced-oxidative-stress-and-promotes-endothelial-repair-through-the-enos-ho-1-pathway
#18
Donghui Liu, Zhenzhen Ding, Mengzhang Wu, Wenqi Xu, Mingming Qian, Qian Du, Le Zhang, Ye Cui, Jianlan Zheng, He Chang, Caihua Huang, Donghai Lin, Yan Wang
Apolipoprotein A-I (apoA-I) mimetic peptide exerts many anti-atherogenic properties. However, the underlying mechanisms related to the endothelial protective effects remain elusive. In this study, the apoA-I mimetic peptide, D-4F, was used. Proliferation assay, wound healing, and transwell migration experiments showed that D-4F improved the impaired endothelial proliferation and migration resulting from ox-LDL. Endothelial adhesion molecules expression and monocyte adhesion assay demonstrated that D-4F inhibited endothelial inflammation...
April 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28257761/membrane-potential-determines-calcium-alternans-through-modulation-of-sr-ca-2-load-and-l-type-ca-2-current
#19
Giedrius Kanaporis, Lothar A Blatter
Alternans is a risk factor for cardiac arrhythmia, including atrial fibrillation. At the cellular level alternans is observed as beat-to-beat alternations in contraction, action potential (AP) morphology and magnitude of the Ca(2+) transient (CaT). It is widely accepted that the bi-directional interplay between membrane voltage and Ca(2+) is crucial for the development of alternans, however recently the attention has shifted to instabilities in cellular Ca(2+) handling, while the role of AP alternation remains poorly understood...
April 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28257760/induction-of-mir133a-expression-by-il-19-targets-ldlrap1-and-reduces-oxldl-uptake-in-vsmc
#20
Khatuna Gabunia, Allison B Herman, Mitali Ray, Sheri E Kelemen, Ross N England, Raul DeLa Cadena, William J Foster, Katherine J Elliott, Satoru Eguchi, Michael V Autieri
The transformation of vascular smooth muscle cells [VSMC] into foam cells leading to increased plaque size and decreased stability is a key, yet understudied step in atherogenesis. We reported that Interleukin-19 (IL-19), a novel, anti-inflammatory cytokine, attenuates atherosclerosis by anti-inflammatory effects on VSMC. In this work we report that IL-19 induces expression of miR133a, a muscle-specific miRNA, in VSMC. Although previously unreported, we report that miR133a can target and reduce mRNA abundance, mRNA stability, and protein expression of Low Density Lipoprotein Receptor Adaptor Protein 1, (LDLRAP1), an adaptor protein which functions to internalize the LDL receptor...
April 2017: Journal of Molecular and Cellular Cardiology
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