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Journal of Molecular and Cellular Cardiology

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https://www.readbyqxmd.com/read/28647341/suppression-of-autophagic-flux-contributes-to-cardiomyocyte-death-by-activation-of-necroptotic-pathways
#1
Makoto Ogasawara, Toshiyuki Yano, Masaya Tanno, Koki Abe, Satoko Ishikawa, Takayuki Miki, Atsushi Kuno, Toshiyuki Tobisawa, Shingo Muratsubaki, Kouhei Ohno, Yuki Tatekoshi, Kei Nakata, Wataru Ohwada, Tetsuji Miura
BACKGROUND: The role of necroptosis in myocardial injury has not been fully characterized. Here we examined roles of mitochondrial permeability transition pore (mPTP) and autophagy in necroptosis of cardiomyocytes. METHODS AND RESULTS: In H9c2 cells, necroptosis was induced by treatment with TNF-α (TNF) and z-VAD-fmk (zVAD) for 24h, and necroptotic death was determined by LDH release (as % of total). TNF/zVAD increased LDH release from 16.6±4.3% to 60.6±2.7%, and the LDH release was suppressed by necrostatin-1 (29...
June 21, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28645752/exercise-training-intensity-and-connexin-43-expression-in-hypertrophic-cardiomyopathy
#2
LETTER
Fabian Sanchis-Gomar, Kabir Malkani, Carme Perez-Quilis
No abstract text is available yet for this article.
June 20, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28641980/cardiomyocyte-specific-overexpression-of-a-37-amino-acid-domain-of-regulator-of-g-protein-signalling-2-inhibits-cardiac-hypertrophy-and-improves-function-in-response-to-pressure-overload-in-mice
#3
Katherine N Lee, Xiangru Lu, Chau Nguyen, Qingping Feng, Peter Chidiac
Regulator of G protein signalling 2 (RGS2) is known to play a protective role in maladaptive cardiac hypertrophy and heart failure via its ability to inhibit Gq and Gs mediated GPCR signalling. We previously demonstrated that RGS2 can also inhibit protein translation and can thereby attenuate cell growth. This G protein-independent inhibitory effect has been mapped to a 37 amino acid domain (RGS2(eb)) within RGS2 that binds to eukaryotic initiation factor 2B (eIF2B). When expressed in neonatal rat cardiomyocytes, RGS2(eb) attenuates both protein synthesis and hypertrophy induced by Gq- and Gs- activating agents...
June 19, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28641979/sexual-dimorphism-in-the-fetal-cardiac-response-to-maternal-nutrient-restriction
#4
Sribalasubashini Muralimanoharan, Cun Li, Ernesto S Nakayasu, Cameron P Casey, Thomas O Metz, Peter W Nathanielsz, Alina Maloyan
Poor maternal nutrition causes intrauterine growth restriction (IUGR); however, its effects on fetal cardiac development are unclear. We have developed a baboon model of moderate maternal undernutrition, leading to IUGR. We hypothesized that the IUGR affects fetal cardiac structure and metabolism. Six control pregnant baboons ate ad-libitum (CTRL)) or 70% CTRL from 0.16 of gestation (G). Fetuses were euthanized at C-section at 0.9G under general anesthesia. Male but not female IUGR fetuses showed left ventricular fibrosis inversely correlated with birth weight...
June 19, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28629760/cardiac-overexpression-of-epac1-in-transgenic-mice-rescues-lipopolysaccharide-induced-cardiac-dysfunction-and-inhibits-jak-stat-pathway
#5
Huiling Jin, Takayuki Fujita, Meihua Jin, Reiko Kurotani, Iyuki Namekata, Shogo Hamaguchi, Yuko Hidaka, Wenqian Cai, Kenji Suita, Yoshiki Ohnuki, Yasumasa Mototani, Kouichi Shiozawa, Rajesh Prajapati, Chen Liang, Masanari Umemura, Utako Yokoyama, Motohiko Sato, Hikaru Tanaka, Satoshi Okumura, Yoshihiro Ishikawa
Pro-inflammatory cytokines are released in septic shock and impair cardiac function via the Jak-STAT pathway. It is well known that sympathetic stimulation leads to coupling of the β-adrenergic receptor/Gs/adenylyl cyclase, a membrane-bound enzyme that catalyzes the conversion of ATP to cAMP, thereby stimulating protein kinase A (PKA) and ultimately compensating for cardiac dysfunction. The mechanism of such compensation by catecholamine has been traditionally understood as PKA-mediated enforcement of cardiac contractility...
June 16, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28623750/lcz696-improves-cardiac-function-via-alleviating-drp1-mediated-mitochondrial-dysfunction-in-mice-with-doxorubicin-induced-dilated-cardiomyopathy
#6
Yan Xia, Zhangwei Chen, Ao Chen, Mingqiang Fu, Zhen Dong, Kai Hu, Xiangdong Yang, Yunzeng Zou, Aijun Sun, Juying Qian, Junbo Ge
AIMS: LCZ696, a novel angiotensin receptor neprilysin inhibitor, is effective in treating heart failure patients. Doxorubicin (DOX) is an effective antitumor medication but the cardiotoxicity limited its clinical use. In this study, we aimed to determine the effect of LCZ696 on DOX-induced cardiomyopathy in mice and in vitro and to explore related mechanisms focusing on fission protein dynamin-related protein 1 (Drp1). METHODS AND RESULTS: In human study, we found that myocardial fission protein Drp1 expression and its ser 616 phosphorylation were significantly increased in dilated cardiomyopathy (DCM) patients...
June 14, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28623080/increased-constitutive-nitric-oxide-production-by-whole-body-periodic-acceleration-ameliorates-alterations-in-cardiomyocytes-associated-with-utrophin-dystrophin-deficiency
#7
Jose R Lopez, Juan Kolster, Rui Zhang, Jose Adams
Duchenne Muscular Dystrophy (DMD) cardiomyopathy is a progressive lethal disease caused by the lack of the dystrophin protein in the heart. The most widely used animal model of DMD is the dystrophin-deficient mdx mouse; however, these mice exhibit a mild dystrophic phenotype with heart failure only late in life. In contrast, mice deficient for both dystrophin and utrophin (mdx/utrn(-/-), or dKO) can be used to model severe DMD cardiomyopathy where pathophysiological indicators of heart failure are detectable by 8-10weeks of age...
June 13, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28600229/the-structural-basis-of-alpha-tropomyosin-linked-asp230asn-familial-dilated-cardiomyopathy
#8
M L Lynn, L Tal Grinspan, T A Holeman, J Jimenez, J Strom, J C Tardiff
Recently, linkage analysis of two large unrelated multigenerational families identified a novel dilated cardiomyopathy (DCM)-linked mutation in the gene coding for alpha-tropomyosin (TPM1) resulting in the substitution of an aspartic acid for an asparagine (at residue 230). To determine how a single amino acid mutation in α-tropomyosin (Tm) can lead to a highly penetrant DCM we generated a novel transgenic mouse model carrying the D230N mutation. The resultant mouse model strongly phenocopied the early onset of cardiomyopathic remodeling observed in patients as significant systolic dysfunction was observed by 2months of age...
June 7, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28587810/subcellular-localization-of-na-k-atpase-isoforms-in-ventricular-myocytes
#9
Garrick K Yuen, Samuel Galice, Donald M Bers
The sodium/potassium ATPase (NKA) is essential for establishing the normal intracellular [Na(+)] and [K(+)] and transmembrane gradients that are essential for many cellular functions, including cardiac electrophysiology and contractility. Different NKA isoforms exhibit differential expression levels, cellular localization, and function in different tissues and species. Prior work has indicated that the NKA-α1 isoform is quantitatively predominant in cardiac myocytes, but that the α2 isoform is preferentially concentrated in the transverse tubules (TT), possibly at junctions with the sarcoplasmic reticulum (SR) where α2 may preferentially modulate cardiac contractility...
June 3, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28576718/effect-of-altered-haemodynamics-on-the-developing-mitral-valve-in-chick-embryonic-heart
#10
Kar Lai Pang, Matthew Parnall, Siobhan Loughna
Intracardiac haemodynamics is crucial for normal cardiogenesis, with recent evidence showing valvulogenesis is haemodynamically dependent and inextricably linked with shear stress. Although valve anomalies have been associated with genetic mutations, often the cause is unknown. However, altered haemodynamics have been suggested as a pathogenic contributor to bicuspid aortic valve disease. Conversely, how abnormal haemodynamics impacts mitral valve development is still poorly understood. In order to analyse altered blood flow, the outflow tract of the chick heart was constricted using a ligature to increase cardiac pressure overload...
May 30, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28554511/induction-of-cardiac-dysfunction-in-developing-and-adult-zebrafish-by-chronic-isoproterenol-stimulation
#11
Mandy Kossack, Selina Hein, Lonny Juergensen, Mauro Siragusa, Alexander Benz, Hugo A Katus, Patrick Most, David Hassel
Zebrafish is a widely used model to evaluate genetic variants and modifiers that can cause heart muscle diseases. Surprisingly, the β-adrenergic receptor (β-AR) pathway in zebrafish is not well characterized, although abnormal β-AR signaling is a major contributor to human heart failure (HF). Chronic β-AR activation in the attempt to normalize heart function in the failing heart results in a reduction of the β-ARs expression and receptor desensitization, largely mediated through G-protein coupled receptor kinase 2 (GRK2) upregulation...
May 26, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28549781/nucleostemin-dysregulation-contributes-to-ischemic-vulnerability-of-diabetic-hearts-role-of-ribosomal-biogenesis
#12
Shihao Zhao, Yunlong Xia, Fuyang Zhang, Zhenyu Xiong, Yueyang Li, Wenjun Yan, Xiyao Chen, Wei Wang, Helin Wang, Erhe Gao, Yan Lee, Congye Li, Shan Wang, Ling Zhang, Ling Tao
Diabetes is a major health problem worldwide. As well-known, diabetes greatly increases cardiac vulnerability to ischemia/reperfusion (I/R) injury, but the underlying mechanisms remain elusive. Nucleostemin (NS) is a nucleolar protein that controls ribosomal biogenesis and exerts cardioprotective effects against I/R injury. However, whether NS-mediated ribosomal biogenesis regulates ischemic vulnerability of diabetic hearts remains unanswered. Utilizing myocardial I/R mouse models, we found that cardiac NS expression significantly increased in response to I/R in normal diet (ND)-fed mice...
May 23, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28546098/altered-long-non-coding-rna-expression-profile-in-rabbit-atria-with-atrial-fibrillation-tcons_00075467-modulates-atrial-electrical-remodeling-by-sponging-mir-328-to-regulate-cacna1c
#13
Zhan Li, Ximin Wang, Weizong Wang, Juanjuan Du, Jinqiu Wei, Yong Zhang, Jiangrong Wang, Yinglong Hou
Electrical remodeling has been reported to play a major role in the initiation and maintenance of atrial fibrillation (AF). Long non-coding RNAs (lncRNAs) have been increasingly recognized as contributors to the pathology of heart diseases. However, the roles and mechanisms of lncRNAs in electrical remodeling during AF remain unknown. In this study, the lncRNA expression profiles of right atria were investigated in AF and non-AF rabbit models by using RNA sequencing technique and validated using quantitative real-time polymerase chain reaction (qRT-PCR)...
May 22, 2017: Journal of Molecular and Cellular Cardiology
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
#14
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 19, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28526246/impaired-mitophagy-facilitates-mitochondrial-damage-in-danon-disease
#15
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
#16
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
#17
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
#18
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
#19
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/28478047/plasma-metabolite-profiles-cellular-cholesterol-efflux-and-non-traditional-cardiovascular-risk-in-patients-with-ckd
#20
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
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