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https://www.readbyqxmd.com/read/28103423/adipose-derived-perivascular-mesenchymal-stromal-stem-cells-promote-functional-vascular-tissue-engineering-for-cardiac-regenerative-purposes
#1
Justin Morrissette-McAlmon, Adriana Blazeski, Sarah Somers, Geran Kostecki, Leslie Tung, Warren L Grayson
Cardiac tissue engineering approaches have the potential to regenerate functional myocardium with intrinsic vascular networks. In this study, we compared the relative effects of human adipose-derived stem/stromal cells (hASCs) and human dermal fibroblasts (hDFs) in co-cultures with neonatal rat ventricular cardiomyocytes (NRVCMs) and human umbilical vein endothelial cells (HUVECs). We found that at the same ratios of NRVCM:hASC and NRVCM:hDF, the hASC co-cultures displayed shorter action potentials and maintained capture at faster pacing rates...
January 19, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28102848/statins-in-anthracycline-induced-cardiotoxicity-rac-and-rho-and-the-heartbreakers
#2
REVIEW
Christian Henninger, Gerhard Fritz
Cancer patients receiving anthracycline-based chemotherapy are at risk to develop life-threatening chronic cardiotoxicity with the pathophysiological mechanism of action not fully understood. Besides the most common hypothesis that anthracycline-induced congestive heart failure (CHF) is mainly caused by generation of reactive oxygen species, recent data point to a critical role of topoisomerase II beta (TOP2B), which is a primary target of anthracycline poisoning, in the pathophysiology of CHF. As the use of the only clinically approved cardioprotectant dexrazoxane has been limited by the FDA in 2011, there is an urgent need for alternative cardioprotective measures...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28102360/modification-of-distinct-ion-channels-differentially-modulates-ca-2-dynamics-in-primary-cultured-rat-ventricular-cardiomyocytes
#3
Xichun Li, Liping Shen, Fang Zhao, Xiaohan Zou, Yuwei He, Fan Zhang, Chunlei Zhang, Boyang Yu, Zhengyu Cao
Primary cultured cardiomyocytes show spontaneous Ca(2+) oscillations (SCOs) which not only govern contractile events, but undergo derangements that promote arrhythmogenesis through Ca(2+) -dependent mechanism. We systematically examined influence on SCOs of an array of ion channel modifiers by recording intracellular Ca(2+) dynamics in rat ventricular cardiomyocytes using Ca(2+) specific fluorescence dye, Fluo-8/AM. Voltage-gated sodium channels (VGSCs) activation elongates SCO duration and reduces SCO frequency while inhibition of VGSCs decreases SCO frequency without affecting amplitude and duration...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28101782/the-antineoplastic-drug-trastuzumab-dysregulates-metabolism-in-ipsc-derived-cardiomyocytes
#4
Brian M Necela, Bianca C Axenfeld, Daniel J Serie, Jennifer M Kachergus, Edith A Perez, E Aubrey Thompson, Nadine Norton
BACKGROUND: The targeted ERBB2 therapy, trastuzumab, has had a tremendous impact on management of patients with HER2+ breast cancer, leading to development and increased use of further HER2 targeted therapies. The major clinical side effect is cardiotoxicity but the mechanism is largely unknown. On the basis that gene expression is known to be altered in multiple models of heart failure, we examined differential gene expression of iPSC-derived cardiomyocytes treated at day 11 with the ERBB2 targeted monoclonal antibody, trastuzumab for 48 h and the small molecule tyrosine kinase inhibitor of EGFR and ERBB2...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28101763/mir-126-affects-brain-heart-interaction-after-cerebral-ischemic-stroke
#5
Jieli Chen, Chengcheng Cui, Xiaoping Yang, Jiang Xu, Poornima Venkat, Alex Zacharek, Peng Yu, Michael Chopp
Cardiovascular diseases are approximately three times higher in patients with neurological deficits than in patients without neurological deficits. MicroRNA-126 (MiR-126) facilitates vascular remodeling and decreases fibrosis and is emerging as an important factor in the pathogenesis of cardiovascular diseases and cerebral stroke. In this study, we tested the hypothesis that decreased miR-126 after ischemic stroke may play an important role in regulating cardiac function. Wild-type (WT), specific conditional-knockout endothelial cell miR-126 (miR-126(EC-/-)), and miR-126 knockout control (miR-126(fl/fl)) mice were subjected to distal middle cerebral artery occlusion (dMCAo) (n = 10/group)...
January 19, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28101702/bone-marrow-very-small-embryonic-like-stem-cells-new-generation-of-autologous-cell-therapy-soon-ready-for-prime-time
#6
EDITORIAL
David M Smadja
Very small embryonic-like stem cells (VSELs) are major pluripotent stem cells described in human and mouse. In this issue of Stem Cell Reviews and Reports, Shaikh and colleagues show in a valuable work that mouse bone marrow collected after 5FU treatment contains VSELs able to undergo in vitro multi-lineage differentiation into cells from all three germ layers and also in germ and hematopoietic cells. These findings are robust since no confounding factor such as feeder cell fusion with VSELs can occur here...
January 18, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28101579/role-of-trna-selenocysteine-1-associated-protein-1-in-the-proliferation-and-apoptosis-of-cardiomyocyte%C3%A2-like-h9c2-cells
#7
Meng-Di Li, Wan-Peng Cheng, Min-Xia Shi, Tang-Dong Ge, Xiao-Lin Zheng, Dong-Yuan Wu, Xiao-Yan Hu, Jin-Cheng Luo, Feng-Lan Li, Hui Li
Transfer RNA selenocysteine 1 associated protein 1 (Trnau1ap) serves an essential role in the synthesis of selenoproteins, which have critical functions in numerous biological processes. Selenium deficiency results in a variety of diseases, including cardiac disease. However, the mechanisms underlying myocardial injury induced by selenium deficiency remain unclear. The present study examined the effects of Trnau1ap under‑ and overexpression in cardiomyocyte‑like H9c2 cells, by transfection with small interfering RNA and an overexpression plasmid, respectively...
February 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28101410/modulation-of-cardiomyocyte-activity-using-pulsed-laser-irradiated-gold-nanoparticles
#8
Lara Gentemann, Stefan Kalies, Michelle Coffee, Heiko Meyer, Tammo Ripken, Alexander Heisterkamp, Robert Zweigerdt, Dag Heinemann
Can photothermal gold nanoparticle mediated laser manipulation be applied to induce cardiac contraction? Based on our previous work, we present a novel concept of cell stimulation. A 532 nm picosecond laser was employed to heat gold nanoparticles on cardiomyocytes. This leads to calcium oscillations in the HL-1 cardiomyocyte cell line. As calcium is connected to the contractility, we aimed to alter the contraction rate of native and stem cell derived cardiomyocytes. A contraction rate increase was particularly observed in calcium containing buffer with neonatal rat cardiomyocytes...
January 1, 2017: Biomedical Optics Express
https://www.readbyqxmd.com/read/28100964/comparative-efficacy-of-nebivolol-and-metoprolol-to-prevent-tachycardia-induced-cardiomyopathy-in-a-porcine-model
#9
Alireza Nazeri, MacArthur A Elayda, Ana Maria Segura, Raymond F Stainback, Joanna Nathan, Vei-Vei Lee, Christina Bove, Luiz Sampaio, Brian Grace, Ali Massumi, Mehdi Razavi
Chronic tachycardia is a well-known cause of nonischemic cardiomyopathy. We hypothesized that nebivolol, a β-blocker with nitric oxide activity, would be superior to a pure β-blocker in preventing tachycardia-induced cardiomyopathy in a porcine model. Fifteen healthy Yucatan pigs were randomly assigned to receive nebivolol, metoprolol, or placebo once a day. All pigs underwent dual-chamber pacemaker implantation. The medication was started the day after the pacemaker implantation. On day 7 after implantation, each pacemaker was set at atrioventricular pace (rate, 170 beats/min), and the pigs were observed for another 7 weeks...
December 2016: Texas Heart Institute Journal
https://www.readbyqxmd.com/read/28100873/microrna-10a-targets-t-box-5-to-inhibit-the-development-of-cardiac-hypertrophy
#10
Dan Wang, Guanqun Zhai, Yangfei Ji, Haiyun Jing
The mechanism of cardiac hypertrophy involving microRNAs (miRNAs) is attracting increasing attention. Our study aimed to investigate the role of miR-10a in cardiac hypertrophy development and the underlying regulatory mechanism.Transverse abdominal aortic constriction (TAAC) surgery was performed to establish a cardiac hypertrophy rat model, and angiotensin II (AngII) was used to induce cardiac hypertrophy in cultured neonatal rat cardiomyocytes. Expression of T-box 5 (TBX5) and miR-10a was altered by cell transfection of siRNA or miRNA mimic/inhibitor...
January 17, 2017: International Heart Journal
https://www.readbyqxmd.com/read/28100487/doxorubicin-induced-nitrosative-stress-is-mitigated-by-vitamin-c-via-the-modulation-of-nitric-oxide-synthases
#11
Gauri Akolkar, Ashim K Bagchi, Prathapan Ayyappan, Davinder S Jassal, Pawan K Singal
An increase in oxidative stress is suggested to be the main cause in Doxorubicin (Dox) -induced cardiotoxicity. However, there is now evidence that activation of inducible nitric oxide synthase (iNOS) and nitrosative stress are also involved. The role of Vitamin C (Vit C) in the regulation of nitric oxide synthase (NOS) and reduction of nitrosative stress in Dox-induced cardiotoxicity is unknown. The present study investigated the effects of Vit C in the mitigation of Dox-induced changes in the levels of nitric oxide (NO), NOS activity, protein expression of NOS isoforms and nitrosative stress as well as cytokines TNFα and IL-10 in isolated cardiomyocytes...
January 18, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28099878/screening-verification-and-analysis-of-biomarkers-for-drug-induced-cardiac-toxicity-in-vitro-based-on-rtca-coupled-with-pcr-array-technology
#12
Lu Zhang, Meng-Xi Xu, Qing-Sheng Yin, Cai-Ying Zhu, Xue-Lian Cheng, Yi-Ran Ren, Peng-Wei Zhuang, Yan-Jun Zhang
Cardiotoxicity is one of the most serious side effects of new drugs. Early detection of the drug induced cardiotoxicity based on the biomarkers provides an important preventative strategy for detecting potential cardiotoxicity of candidate drugs. In this study, we aim to identify the predictive genomics biomarkers for drug-induced cardiac toxicity based on the RTCA coupled with PCR Array technology in primary cells. Three prototypical cardiotoxic compounds (doxorubicin, isoproterenol, ouabain) with different mechanisms were firstly real-time monitored to diagnose the cytotoxicity by using the RTCA, while the functional alterations of cardiomyocytes were also monitored by analyzing the beating frequency of cardiomyocytes...
January 15, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28099512/age-dependent-oxidative-dna-damage-does-not-correlate-with-reduced-proliferation-of-cardiomyocytes-in-humans
#13
Yanhui Huang, Haifa Hong, Minghui Li, Jinfen Liu, Chuan Jiang, Haibo Zhang, Lincai Ye, Jinghao Zheng
BACKGROUND: Postnatal human cardiomyocyte proliferation declines rapidly with age, which has been suggested to be correlated with increases in oxidative DNA damage in mice and plays an important role in regulating cardiomyocyte proliferation. However, the relationship between oxidative DNA damage and age in humans is unclear. METHODS: Sixty right ventricular outflow myocardial tissue specimens were obtained from ventricular septal defect infant patients during routine congenital cardiac surgery...
2017: PloS One
https://www.readbyqxmd.com/read/28098811/aspalathin-protects-the-heart-against-hyperglycemia-induced-oxidative-damage-by-up-regulating-nrf2-expression
#14
Phiwayinkosi V Dludla, Christo J F Muller, Elizabeth Joubert, Johan Louw, M Faadiel Essop, Kwazi B Gabuza, Samira Ghoor, Barbara Huisamen, Rabia Johnson
Aspalathin (ASP) can protect H9c2 cardiomyocytes against high glucose (HG)-induced shifts in myocardial substrate preference, oxidative stress, and apoptosis. The protective mechanism of ASP remains unknown. However, as one of possible, it is well known that phytochemical flavonoids reduce oxidative stress via nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activation resulting in up-regulation of antioxidant genes and enzymes. Therefore, we hypothesized that ASP protects the myocardium against HG- and hyperglycemia-induced oxidative damage by up-regulating Nrf2 expression in H9c2 cardiomyocytes and diabetic (db/db) mice, respectively...
January 14, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28098558/platelet-derived-growth-factor-pdgf-signaling-directs-cardiomyocyte-movement-toward-the-midline-during-heart-tube-assembly
#15
Joshua Bloomekatz, Reena Singh, Owen Wj Prall, Ariel C Dunn, Megan Vaughan, Chin-San Loo, Richard P Harvey, Deborah Yelon
Communication between neighboring tissues plays a central role in guiding organ morphogenesis. During heart tube assembly, interactions with the adjacent endoderm control the medial movement of cardiomyocytes, a process referred to as cardiac fusion. However, the molecular underpinnings of this endodermal-myocardial relationship remain unclear. Here, we show an essential role for platelet-derived growth factor receptor alpha (Pdgfra) in directing cardiac fusion. Mutation of pdgfra disrupts heart tube assembly in both zebrafish and mouse...
January 18, 2017: ELife
https://www.readbyqxmd.com/read/28098423/brain-derived-neurotrophic-factor-attenuates-doxorubicin-induced-cardiac-dysfunction-through-activating-akt-signalling-in-rats
#16
Pengzhou Hang, Jing Zhao, Li Sun, Minghui Li, Yu Han, Zhimin Du, Yue Li
The clinical application of doxorubicin (Dox) is limited by its adverse effect of cardiotoxicity. Previous studies have suggested the cardioprotective effect of brain-derived neurotrophic factor (BDNF). We hypothesize that BDNF could protect against Dox-induced cardiotoxicity. Sprague Dawley rats were injected with Dox (2.5 mg/kg, 3 times/week, i.p.), in the presence or absence of recombinant BDNF (0.4 μg/kg, i.v.) for 2 weeks. H9c2 cells were treated with Dox (1 μM) and/or BDNF (400 ng/ml) for 24 hrs. Functional roles of BDNF against Dox-induced cardiac injury were examined both in vivo and in vitro...
November 7, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28096472/myosin-vi-facilitates-connexin-43-gap-junction-accretion
#17
Bennett Waxse, Prabuddha Sengupta, Geoffrey G Hesketh, Jennifer Lippincott-Schwartz, Folma Buss
In this study, we demonstrate myosin VI enrichment at Cx43 gap junctions in heart tissue, primary cardiomyocytes and cell culture models. The loss of myosin VI via siRNA-mediated knock down or isolation of primary cardiac tissue and fibroblasts from the myosin VI-null mouse results in reduced GJ plaque size with a concomitant reduction in intercellular communication as shown by FRAP and a new method of selective calcein administration. Analysis of the molecular role of myosin VI in Cx43 trafficking indicates that myosin VI is dispensable in the delivery of Cx43 to the cell surface and connexon movement in the plasma membrane...
January 17, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28096415/increased-mitochondrial-nanotunneling-activity-induced-by-calcium-imbalance-affects-intermitochondrial-matrix-exchanges
#18
Manuela Lavorato, V Ramesh Iyer, Williams Dewight, Ryan R Cupo, Valentina Debattisti, Ludovic Gomez, Sergio De la Fuente, Yan-Ting Zhao, Héctor H Valdivia, György Hajnóczky, Clara Franzini-Armstrong
Exchanges of matrix contents are essential to the maintenance of mitochondria. Cardiac mitochondrial exchange matrix content in two ways: by direct contact with neighboring mitochondria and over longer distances. The latter mode is supported by thin tubular protrusions, called nanotunnels, that contact other mitochondria at relatively long distances. Here, we report that cardiac myocytes of heterozygous mice carrying a catecholaminergic polymorphic ventricular tachycardia-linked RyR2 mutation (A4860G) show a unique and unusual mitochondrial response: a significantly increased frequency of nanotunnel extensions...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096338/mitochondrial-fusion-dynamics-is-robust-in-the-heart-and-depends-on-calcium-oscillations-and-contractile-activity
#19
Verónica Eisner, Ryan R Cupo, Erhe Gao, György Csordás, William S Slovinsky, Melanie Paillard, Lan Cheng, Jessica Ibetti, S R Wayne Chen, J Kurt Chuprun, Jan B Hoek, Walter J Koch, György Hajnóczky
Mitochondrial fusion is thought to be important for supporting cardiac contractility, but is hardly detectable in cultured cardiomyocytes and is difficult to directly evaluate in the heart. We overcame this obstacle through in vivo adenoviral transduction with matrix-targeted photoactivatable GFP and confocal microscopy. Imaging in whole rat hearts indicated mitochondrial network formation and fusion activity in ventricular cardiomyocytes. Promptly after isolation, cardiomyocytes showed extensive mitochondrial connectivity and fusion, which decayed in culture (at 24-48 h)...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096202/hasf-c3orf58-is-a-novel-ligand-of-the-insulin-like-growth-factor-1-receptor
#20
Akshay Bareja, Conrad Hodgkinson, Alan Payne, Richard Pratt, Victor Dzau
We have recently shown that Hypoxia and Akt induced Stem cell Factor (HASF) protects the heart from ischemia-induced damage and promotes cardiomyocyte proliferation. While we have identified certain signaling pathways responsible for these protective effects, the receptor mediating these effects was unknown. Here, we undertook studies to identify the HASF receptor. A yeast two-hybrid screen identified a partial fragment of Insulin-like Growth Factor 1 Receptor (IGF1R) as a binding partner of HASF. Subsequent co-immunoprecipitation experiments showed that HASF bound to full-length IGF1R...
January 17, 2017: Biochemical Journal
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