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https://www.readbyqxmd.com/read/28329361/sex-hormones-affect-outcome-in-arrhythmogenic-right-ventricular-cardiomyopathy-dysplasia-from-a-stem-cell-derived-cardiomyocyte-based-model-to-clinical-biomarkers-of-disease-outcome
#1
Deniz Akdis, Ardan M Saguner, Khooshbu Shah, Chuanyu Wei, Argelia Medeiros-Domingo, Arnold von Eckardstein, Thomas F Lüscher, Corinna Brunckhorst, H S Vincent Chen, Firat Duru
Aims: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is characterized by fibrofatty infiltration of the myocardium and ventricular arrhythmias that may lead to sudden cardiac death. It has been observed that male patients develop the disease earlier and present with more severe phenotypes as compared to females. Thus, we hypothesized that serum levels of sex hormones may contribute to major arrhythmic cardiovascular events (MACE) in patients with ARVC/D. Methods and results: The serum levels of five sex hormones, sex hormone-binding globulin, high sensitivity troponin T, pro-brain natriuretic peptide, cholesterol, triglycerides, insulin, and glucose were measured in 54 ARVC/D patients (72% male)...
February 18, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28327633/cardiac-drug-drug-interaction-between-hcv-ns5b-pronucleotide-inhibitors-and-amiodarone-is-determined-by-their-specific-diastereochemistry
#2
Armando Lagrutta, Christopher P Regan, Haoyu Zeng, John P Imredy, Kenneth Koeplinger, Pierre Morissette, Liping Liu, Gordon Wollenberg, Christopher Brynczka, José Lebrón, Joseph DeGeorge, Frederick Sannajust
Severe bradycardia/bradyarrhythmia following coadministration of the HCV-NS5B prodrug sofosbuvir with amiodarone was recently reported. Our previous preclinical in vivo experiments demonstrated that only certain HCV-NS5B prodrugs elicit bradycardia when combined with amiodarone. In this study, we evaluate the impact of HCV-NS5B prodrug phosphoramidate diastereochemistry (D-/L-alanine, R-/S-phosphoryl) in vitro and in vivo. Co-applied with amiodarone, L-ala,SP prodrugs increased beating rate and decreased beat amplitude in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), but D-ala,RP produgs, including MK-3682, did not...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28327614/partial-reprogramming-of-pluripotent-stem-cell-derived-cardiomyocytes-into-neurons
#3
Wenpo Chuang, Arun Sharma, Praveen Shukla, Guang Li, Moritz Mall, Kuppusamy Rajarajan, Oscar J Abilez, Ryoko Hamaguchi, Joseph C Wu, Marius Wernig, Sean M Wu
Direct reprogramming of somatic cells has been demonstrated, however, it is unknown whether electrophysiologically-active somatic cells derived from separate germ layers can be interconverted. We demonstrate that partial direct reprogramming of mesoderm-derived cardiomyocytes into neurons is feasible, generating cells exhibiting structural and electrophysiological properties of both cardiomyocytes and neurons. Human and mouse pluripotent stem cell-derived CMs (PSC-CMs) were transduced with the neurogenic transcription factors Brn2, Ascl1, Myt1l and NeuroD...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28327605/ginsenoside-rb1-protects-against-ischemia-reperfusion-induced-myocardial-injury-via-energy-metabolism-regulation-mediated-by-rhoa-signaling-pathway
#4
Yuan-Chen Cui, Chun-Shui Pan, Li Yan, Lin Li, Bai-He Hu, Xin Chang, Yu-Ying Liu, Jing-Yu Fan, Kai Sun, Quan -Li, Jing-Yan Han
Cardiac ischemia and reperfusion (I/R) injury remains a challenge for clinicians. Ginsenoside Rb1 (Rb1) has been reported to have the ability to attenuate I/R injury, but its effect on energy metabolism during cardiac I/R and the underlying mechanism remain unknown. In this study, we detected the effect of Rb1 on rat myocardial blood flow, myocardial infarct size, cardiac function, velocity of venule red blood cell, myocardial structure and apoptosis, energy metabolism and change in RhoA signaling pathway during cardiac I/R injury...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28326674/whole-exome-sequencing-with-genomic-triangulation-implicates-cdh2-encoded-n-cadherin-as-a-novel-pathogenic-substrate-for-arrhythmogenic-cardiomyopathy
#5
Kari L Turkowski, David J Tester, J Martijn Bos, Kristina H Haugaa, Michael J Ackerman
BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) is a heritable disease characterized by fibrofatty replacement of cardiomyocytes, has a prevalence of approximately 1 in 5000 individuals, and accounts for approximately 20% of sudden cardiac death in the young (≤35 years). ACM is most often inherited as an autosomal dominant trait with incomplete penetrance and variable expression. While mutations in several genes that encode key desmosomal proteins underlie about half of all ACM, the remainder is elusive genetically...
March 21, 2017: Congenital Heart Disease
https://www.readbyqxmd.com/read/28326207/dasatinib-and-prednisolone-induction-therapy-for-a-case-of-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-with-dilated-cardiomyopathy-accompanied-by-life-threatening-ventricular-tachycardia
#6
Mitsutaka Nishimoto, Hirohisa Nakamae, Kana Matsumoto, Kunihiko Morita, Yuki Koga, Dai Momose, Masayuki Hino
A 56-year-old man being treated for dilated cardiomyopathy presented with epigastralgia. He was diagnosed with ventricular tachycardia and Philadelphia chromosome-positive acute lymphoblastic leukemia. After treating incessant ventricular tachycardia, we commenced induction therapy for leukemia with dasatinib and prednisolone to minimize toxicity towards cardiomyocytes and the cardiac conduction system. Although dasatinib was temporarily withheld because of a recurrence of ventricular tachycardia, we rechallenged dasatinib while using bisoprolol and amiodarone and achieved a complete hematological response three weeks later...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28325684/monitoring-and-visualizing-microrna-dynamics-during-live-cell-differentiation-using-microrna-responsive-non-viral-reporter-vectors
#7
Hideyuki Nakanishi, Kenji Miki, Kaoru R Komatsu, Masayuki Umeda, Megumi Mochizuki, Azusa Inagaki, Yoshinori Yoshida, Hirohide Saito
MicroRNA (miRNA) activity differs with cell type, suggesting it can be used as a cell marker. In this study, we developed novel miRNA-responsive non-viral reporter vectors to continuously monitor and visualize miRNA dynamics during differentiation and to efficiently purify target living cells. Each vector codes miRNA-responsive and reference reporter genes in a single mRNA. These two genes are independent modules but transcribed by a single promoter, which enables us to distinguish miRNA-mediated post-transcriptional repression from transcriptional repression...
March 2, 2017: Biomaterials
https://www.readbyqxmd.com/read/28322254/stk38-modulates-rbm24-protein-stability-to-regulate-sarcomere-assembly-in-cardiomyocytes
#8
Jing Liu, Xu Kong, Lee Yew Mun, Zhang Meng Kai, Guo Li Yan, Yu Lin, Teck Kwang Lim, Qingsong Lin, Xiu Qin Xu
RNA-binding protein Rbm24 is a key regulator of heart development and required for sarcomere assembly and heart contractility. Yet, its underlying mechanism remains unclear. Here, we link serine/threonine kinase 38 (Stk38) signaling to the regulation of Rbm24 by showing that Rbm24 phosphorylation and its function could be modulated by Stk38. Using co-immunoprecipitation coupled with mass spectrometry technique, we identified Stk38 as an endogenous binding partner of Rbm24. Stk38 knockdown resulted in decreased Rbm24 protein level in cardiomyocytes...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28321644/vinpocetine-attenuates-pathological-cardiac-remodeling-by-inhibiting-cardiac-hypertrophy-and-fibrosis
#9
Mei-Ping Wu, Yi-Shuai Zhang, Xiangbin Xu, Qian Zhou, Jian-Dong Li, Chen Yan
PURPOSE: Pathological cardiac remodeling, characterized by cardiac hypertrophy and fibrosis, is a pathological feature of many cardiac disorders that leads to heart failure and cardiac arrest. Vinpocetine, a derivative of the alkaloid vincamine, has been used for enhancing cerebral blood flow to treat cognitive impairment. However, its role in pathological cardiac remodeling remains unknown. The aim of this study is to examine the effect of vinpocetine on pathological cardiac remodeling induced by chronic stimulation with angiotensin II (Ang II)...
March 20, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28321411/different-densities-of-na-ca-exchange-current-in-t-tubular-and-surface-membranes-and-their-impact-on-cellular-activity-in-a-model-of-rat-ventricular-cardiomyocyte
#10
M Pásek, J Šimurda, G Christé
The ratio of densities of Na-Ca exchanger current (INaCa) in the t-tubular and surface membranes (INaCa-ratio) computed from the values of INaCa and membrane capacitances (Cm) measured in adult rat ventricular cardiomyocytes before and after detubulation ranges between 1.7 and 25 (potentially even 40). Variations of action potential waveform and of calcium turnover within this span of the INaCa-ratio were simulated employing previously developed model of rat ventricular cell incorporating separate description of ion transport systems in the t-tubular and surface membranes...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28321239/xinfuli-improves-cardiac-function-histopathological-changes-and-attenuate-cardiomyocyte-apoptosis-in-rats-with-doxorubicin-induced-cardiotoxicity
#11
Pei-Pei Lu, Jie Ma, Xiao-Peng Liang, Cai-Xia Guo, Yan-Kun Yang, Kun-Qi Yang, Qi-Ming Shen, Li-Hong Ma, Xian-Liang Zhou
BACKGROUND: Xinfuli Granule (XG), a compound Chinese herbal medicine, has been effectively used in China for the treatment of heart failure for more than fifty years. This study aimed to investigate the effects and the underlying mechanisms of Xinfuli in rats with doxorubicin-induced cardiotoxicity. METHODS: Sprague-Dawley rats were treated with intraperitoneal injection of Doxorubicin (DOX, 2.5 mg/kg per week) for six weeks, and then randomly divided into four groups which received intragastrically administration of normal saline (control group) or different dosage of XG (0...
December 2016: Journal of Geriatric Cardiology: JGC
https://www.readbyqxmd.com/read/28321048/evaluation-of-the-effects-of-power-frequency-magnetic-fields-on-the-electrical-activity-of-cardiomyocytes-differentiated-from-human-induced-pluripotent-stem-cells
#12
Masayuki Takahashi, Atsushi Saito, Yasuhiko Jimbo, Satoshi Nakasono
Although cardiac activity is known to differ between species in many respects, most evaluations of the cardiac effects of low-frequency electric and magnetic fields, which have a stimulant effect on electrically activated cells, have been performed in non-human experimental animals and cells, and the effects in humans have been assessed using theoretical models. In recent years, it has been verified that human cardiomyocytes differentiated from human induced pluripotent stem cells (hiPS-CM) are useful for evaluating human responses to various cardioactive compounds...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28321045/characterization-of-human-ips-cell-derived-cardiomyocyte-sheets-as-a-model-to-detect-drug-induced-conduction-disturbance
#13
Hiroko Izumi-Nakaseko, Yuji Nakamura, Takeshi Wada, Kentaro Ando, Yasunari Kanda, Yuko Sekino, Atsushi Sugiyama
In order to characterize human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) sheets as a model for detecting drug-induced conduction disturbance, we examined their electrophysiological and electropharmacological properties by using the multi-electrode array system with a programmed electrical stimulation protocol. At pre-drug control, the conduction speed, effective refractory period and field potential duration were 0.14 ± 0.01 m/sec, 453 ± 10 msec and 361 ± 9 msec, respectively at a cycle length of 1,000 msec (n = 18)...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28321024/the-growth-hormone-secretagogue-hexarelin-protects-rat-cardiomyocytes-from-in-vivo-ischemia-reperfusion-injury-through-interleukin-1-signaling-pathway
#14
Jiannan Huang, Yi Li, Juan Zhang, Yusheng Liu, Qinghua Lu
Hexarelin, a synthetic growth hormone-releasing peptide, has been proven to possess cardioprotective actions through its binding to the growth hormone secretagogue receptor (GHSR) 1a and the non-GHSR receptor CD36. However, its effect on myocardial ischemia/reperfusion (I/R) injury has not been fully clarified in vivo. We aimed to determine whether hexarelin treatment could protect cardiomyocytes from I/R injury and to examine the underlying mechanisms. In vivo hearts of male SD rats underwent 30 minutes of ischemia by left coronary artery ligation followed by reperfusion...
March 17, 2017: International Heart Journal
https://www.readbyqxmd.com/read/28320863/rac1-gtpase-regulates-11%C3%AE-hydroxysteroid-dehydrogenase-type-2-and-fibrotic-remodeling
#15
Daniel Lavall, Pia Schuster, Nadine Jacobs, Andrey Kazakov, Michael Böhm, Ulrich Laufs
The aim of the study was to characterize the role of Rac1 GTPase for the mineralocorticoid receptor (MR) mediated pro-fibrotic remodeling. Transgenic mice with cardiac overexpression of constitutively active Rac1 (RacET) develop an age-dependent phenotype with atrial dilatation, fibrosis and atrial fibrillation. Expression of MR was similar in RacET and wild-type (WT) mice. The expression of 11β hydroxysteroid dehydrogenase type 2 (11β-HSD2) was age-dependently upregulated in the atria and the left ventricles of RacET mice on mRNA and protein level...
March 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28320859/2-arachidonoylglycerol-ameliorates-inflammatory-stress-induced-insulin-resistance-in-cardiomyocytes
#16
Dipanjan Chanda, Yvonne Oligschlaeger, Ilvy Geraets, Yilin Liu, Xiaoqing Zhu, Jieyi Li, Miranda Nabben, Will Coumans, Joost J F P Luiken, Jan F C Glatz, Dietbert Neumann
Several studies have linked impaired glucose uptake and insulin resistance (IR) to functional impairment of the heart. Recently, endocannabinoids have been implicated in cardiovascular disease. However, the mechanisms involving endocannabinoid signaling, glucose uptake and IR in cardiomyocytes are understudied. Here, we report the endocannabinoid 2-Arachidonoylglycerol (2-AG) via stimulation of cannabinoid type-1 (CB1) receptor and Ca2+/Calmodulin-dependent protein kinase β (CaMKKβ) activates AMPK leading to increased glucose uptake...
March 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28323971/n-acetylcysteine-prevents-low-t3-syndrome-and-attenuates-cardiac-dysfunction-in-a-male-rat-model-of-myocardial-infarction
#17
Tatiana Ederich Lehnen, Marcus Vinicius Santos, Adrio Lima, Ana Luiza Maia, Simone Magagnin Wajner
Nonthyroidal illness syndrome (NTIS) affects patients with myocardial infarction (MI). Oxidative stress has been implicated as a causative factor of NTIS, and reversed via N-acetylcysteine (NAC). Male Wistar rats submitted to left anterior coronary artery occlusion received NAC or placebo. Decreases in T3 levels were noted in MI-placebo at 10 and 28 days post-MI, but not in MI-NAC. Groups exhibited similar infarct areas whereas MI-NAC exhibited higher ejection fraction (EF) than MI-placebo. Left ventricular systolic (LVSd) and diastolic (LVDd) diameters were also preserved in MI-NAC, but not in MI-placebo...
February 17, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323876/pim1-minicircle-as-a-therapeutic-treatment-for-myocardial-infarction
#18
Nan Liu, Bingyan J Wang, Kathleen M Broughton, Roberto Alvarez, Sailay Siddiqi, Rebeca Loaiza, Nicky Nguyen, Pearl Quijada, Natalie Gude, Mark A Sussman
PIM1, a pro-survival gene encoding a serine/ threonine kinase, influences cell proliferation and survival. Modification of cardiac progenitor cells (CPCs) or cardiomyocytes with PIM1 using a lentivirus-based delivery method showed long-term improved cardiac function after myocardial infarction (MI). However, lentivirus based delivery methods have stringent FDA regulation with respect to clinical trials. To provide an alternative and low risk PIM1 delivery method, this study examined the use of a non-viral modified plasmid-minicircle (MC) as a vehicle to deliver PIM1 into mouse CPCs (mCPCs) in vitro and the myocardium in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28323425/structure-based-design-of-highly-selective-and-potent-g-protein-coupled-receptor-kinase-2-inhibitors-based-on-paroxetine
#19
Helen V Waldschmidt, Kristoff T Homan, Marilyn C Cato, Osvaldo Cruz-Rodríguez, Alessandro Cannavo, Michael W Wilson, Jianliang Song, Joseph Y Cheung, Walter J Koch, John J G Tesmer, Scott D Larsen
In heart failure, the β-adrenergic receptors (βARs) become desensitized and uncoupled from heterotrimeric G proteins. This process is initiated by G protein-coupled receptor kinases (GRKs), some of which are upregulated in the failing heart making them desirable therapeutic targets. The selective serotonin reuptake inhibitor, paroxetine, was previously identified as a GRK2 inhibitor. Utilizing a structure based drug design approach we modified paroxetine to generate a small compound library. Included in this series is a highly potent and selective GRK2 inhibitor, 14as, with an IC50 of 30 nM against GRK2 and greater than 230-fold selectivity over other GRKs and kinases...
March 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28320040/mitochondria-as-a-target-for-the-cardioprotective-effects-of-cydonia-oblonga-mill-and-ficus-carica-l-in-doxorubicin-induced-cardiotoxicity
#20
Saman Gholami, Mir-Jamal Hosseini, Leila Jafari, Fatemeh Omidvar, Mohammad Kamalinejad, Vida Mashayekhi, Seyed Hojjat Hosseini, Azin Kardan, Jalal Pourahmad, Mohammad Reza Eskandari
Quince (Cydonia oblonga Mill.) and fig (Ficus carica L.) exhibit a broad spectrum of pharmacological activities. Regarding the cardiotoxic effect of doxorubicin (DOX) is mediated mainly through mitochondrial oxidative stress and dysfunction; the present study evaluated the cardioprotective effects of the aqueous extracts of Cydonia oblonga Mill. fruit (ACO) and Ficus carica L. fruit (AFC) against DOX-induced cardiotoxicity. Cardiomyocytes toxicity was induced in male Sprague Dawley rats by intraperitoneal (ip) injections of 2...
March 20, 2017: Drug Research
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