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https://www.readbyqxmd.com/read/28427897/boosters-and-barriers-for-direct-cardiac-reprogramming
#1
REVIEW
Mahmood Talkhabi, Elmira Rezaei Zonooz, Hossein Baharvand
Heart disease is currently the most significant cause of morbidity and mortality worldwide, which accounts for approximately 33% of all deaths. Recently, a promising and alchemy-like strategy has been developed called direct cardiac reprogramming, which directly converts somatic cells such as fibroblasts to cardiac lineage cells such as cardiomyocytes (CMs), termed induced CMs or iCMs. The first in vitro cardiac reprogramming study, mediated by cardiac transcription factors (TFs)-Gata4, Tbx5 and Mef2C-, was not enough efficient to produce an adequate number of fully reprogrammed, functional iCMs...
April 17, 2017: Life Sciences
https://www.readbyqxmd.com/read/28426026/generation-of-multipotent-induced-cardiac-progenitor-cells-from-mouse-fibroblasts-and-potency-testing-in-ex-vivo-mouse-embryos
#2
Pratik A Lalit, Adriana M Rodriguez, Karen M Downs, Timothy J Kamp
Here we describe a protocol to generate expandable and multipotent induced cardiac progenitor cells (iCPCs) from mouse adult fibroblasts using forced expression of Mesp1, Tbx5, Gata4, Nkx2.5 and Baf60c (MTGNB) along with activation of Wnt and JAK/STAT signaling. This method does not use iPS cell factors and thus differs from cell activation and signaling-directed (CASD) reprogramming to cardiac progenitors. Our method is specific to direct CPC reprogramming, whereas CASD reprogramming can generate various cell types depending on culture conditions and raises the possibility of transitioning through a pluripotent cell state...
May 2017: Nature Protocols
https://www.readbyqxmd.com/read/28414055/dihydromyricetin-attenuated-ang-ii-induced-cardiac-fibroblasts-proliferation-related-to-inhibitory-of-oxidative-stress
#3
Qiuyi Song, Lulu Liu, Jin Yu, Jingyao Zhang, Mengting Xu, Linlin Sun, Huiqin Luo, Zhaosong Feng, Guoliang Meng
Dihydromyricetin (DMY) is one of the most important flavonoids in vine tea, which showed several pharmacological effects. However, information about the potential role of DMY on angiotensin II (Ang II) induced cardiac fibroblasts proliferation remains unknown. In the present study, cardiac fibroblasts isolated from neonatal Sprague-Dawley rats were pretreated with different concentrations of DMY (0- 320μM) for 4h, or DMY (80μM) for different time (0-24h), followed by Ang II (100nM) stimulation for 24h, Then number of cardiac fibroblasts and content of hydroxyproline was measured...
April 13, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28412345/a-novel-identified-circular-rna-circrna_010567-promotes-myocardial-fibrosis-via-suppressing-mir-141-by-targeting-tgf-%C3%AE-1
#4
Bing Zhou, He-Yun Xu
Circular RNAs (circRNAs) are a novel type of endogenous noncoding RNA gaining research interest in recent years. Despite this increase in interest, the mechanism of circRNAs in the pathogenesis of multiple cardiovascular diseases, particularly myocardial fibrosis, is rarely reported. In the following study, the expression profiles and potential mechanisms of circRNAs in mice myocardial fibrosis models in vitro are investigated. Previous research examining circRNA expression profiles of diabetic db/db mice myocardium using circRNA microarray found 43 circRNAs were abnormally expressed, including 24 up-regulated circRNAs and 19 down-regulated circRNAs...
April 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28411247/exosomal-microrna-transfer-into-macrophages-mediates-cellular-postconditioning
#5
Geoffrey de Couto, Romain Gallet, Linda Cambier, Ervin Jaghatspanyan, Nupur Makkar, James Frederick Dawkins, Benjamin P Berman, Eduardo Marbán
BACKGROUND: Cardiosphere-derived cells (CDCs) confer cardioprotection in acute myocardial infarction (MI) via distinctive macrophage (MΦ) polarization. Here we demonstrate that CDC-secreted exosomes (CDCexo) recapitulate the cardioprotective effects of CDC therapy known as cellular postconditioning. METHODS: Rats and pigs underwent MI induced by ischemia-reperfusion prior to intracoronary infusion of CDCexo, inert fibroblast exosomes (Fbexo; control), or vehicle. Two days later, infarct size was quantified...
April 14, 2017: Circulation
https://www.readbyqxmd.com/read/28404615/myeloperoxidase-mediates-postischemic-arrhythmogenic-ventricular-remodeling
#6
Martin Mollenhauer, Kai Friedrichs, Max Lange, Jan Gesenberg, Lisa Remane, Christina Kerkenpaß, Jenny Krause, Johanna Schneider, Thorben Ravekes, Martina Maass, Marcel Halbach, Gabriel Peinkofer, Tomo Saric, Dennis Mehrkens, Matti Adam, Florian G Deuschl, Denise Lau, Birgit Geertz, Kashish Manchanda, Thomas Eschenhagen, Lukas Kubala, Tanja K Rudolph, Yuping Wu, Wh W Tang, Stanley L Hazen, Stephan Baldus, Anna Klinke, Volker Rudolph
Rationale: Ventricular arrhythmias remain the leading cause of death in patients suffering myocardial ischemia. Myeloperoxidase (MPO), a heme-enzyme released by polymorphonuclear neutrophils, accumulates within ischemic myocardium and has been linked to adverse left ventricular remodeling. Objective: To reveal the role of MPO for the development of ventricular arrhythmias. Methods and Results: In different murine models of myocardial ischemia MPO deficiency profoundly decreased vulnerability for ventricular tachycardia (VT) upon programmed right ventricular and burst stimulation and spontaneously as assessed by ECG telemetry following isoproterenol injection...
April 12, 2017: Circulation Research
https://www.readbyqxmd.com/read/28402974/cardiac-changes-and-their-association-with-fetuin-a-and-fibroblast-growth-factor-23-in-children-with-chronic-kidney-disease
#7
Abdullahi Mudi, Hopewell Ntsinjana, Caroline Dickens, Cecil Levy, Daynia Ballot
AIMS: In children with chronic kidney disease (CKD), fetuin-A and fibroblast growth factor-23 (FGF-23) have been implicated in the mechanism and progression of several cardiac changes. This study aimed to determine the types and rates of cardiac changes in children with CKD and their association with fetuin-A, FGF-23, and other cardiovascular risk factors (CVRFs). METHODS: This comparative cross-sectional study recruited 88 children (5-18 years): 27 CKD I with a glomerular filtration rate (GFR) >90 mL/min/1...
April 13, 2017: Nephron
https://www.readbyqxmd.com/read/28397812/upregulation-of-sestrins-protect-atriums-against-oxidative-damage-and-fibrosis-in-human-and-experimental-atrial-fibrillation
#8
Zengxiang Dong, Chaolan Lin, Yujiao Liu, Hongbo Jin, Hong Wu, Zhenjun Li, Liping Sun, Lu Zhang, Xi Hu, Yingying Wei, Chengcheng Wang, Wei Han
Atrial Fibrillation (AF) is common in the elderly and Sestrins (Sesns) have been suggested to prevent age-related pathologies. The aim of this study was to investigate the effects of Sesns in AF. Clinical data were collected and a small sample of atrial appendage and atrium was obtained from patients undergoing valve repairment. The expression of Sesn1, Sesn2, and Sesn3 was significantly higher in patients with permanent atrial fibrillation (PmAF) than that in sinus rhythm (SR), and further greater in the left atrium than the right in PmAF patients...
April 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28397099/maturation-of-human-pluripotent-stem-cell-derived-cardiomyocytes-is-improved-in-cardiovascular-construct
#9
Hanna Vuorenpää, Kirsi Penttinen, Tuula Heinonen, Mari Pekkanen-Mattila, Jertta-Riina Sarkanen, Timo Ylikomi, Katriina Aalto-Setälä
In order to translate preclinical data into the clinical studies, relevant in vitro models with structure and key functional properties similar to native human tissue should be used. In vitro cardiac models with vascular structures mimic the highly vascularized myocardium and provide interactions between endothelial cells, stromal cells and cardiomyocytes. Currently, human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have been shown to present immature morphology and fetal-like electrophysiological properties that may limit their use as physiological test platform...
April 10, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28393175/trpm7-channels-mediate-the-functional-changes-in-cardiac-fibroblasts-induced-by-angiotensin-ii
#10
Sha Li, Mingjiang Li, Xin Yi, Furong Guo, Yanli Zhou, Suqin Chen, Xian Wu
Transient receptor potential melastatin 7 (TRPM7), a bifunctional channel protein owning both cation permeability and kinase activity, plays an important role in the pathophysiological process of many cell types, such as vascular smooth muscle cells, human glioma cells and mouse cortical astrocytes. However, whether TRPM7 channels play a key role in the functional change of cardiac fibroblasts (CFs) induced by angiotensin II (Ang II) remains unknown. Using Cell Counting Kit-8 (CCK-8) assay, immunofluorescence assay, western blot analysis, RT-qPCR, RNA interference (RNAi) and whole-cell patch-clamp techniques, the present study aimed to explore the role of TRPM7 channels in the proliferation, differentiation and collagen synthesis of CFs induced by Ang II...
April 6, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28391633/comparisons-of-cardioprotective-efficacy-between-fibroblast-growth-factor-21-and-dipeptidyl-peptidase-4-inhibitor-in-pre-diabetic-rats
#11
Pongpan Tanajak, Piangkwan Sa-Nguanmoo, Nattayaporn Apaijai, Xiaojie Wang, Guang Liang, Xiaokun Li, Chao Jiang, Siriporn C Chattipakorn, Nipon Chattipakorn
AIMS: Comparative efficacy between fibroblast growth factor 21 (FGF21) and vildagliptin on metabolic regulation, cardiac mitochondrial function, heart rate variability (HRV) and left ventricular (LV) function is not known. We hypothesized that FGF21 and vildagliptin share a similar efficacy in improving these parameters in high-fat diet (HFD) induced obese-insulin resistant rats. METHODS: Twenty-four male Wistar rats were fed with either a normal diet (ND) or a HFD for 12 weeks...
April 9, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28389873/molecular-barriers-to-direct-cardiac-reprogramming
#12
REVIEW
Haley Vaseghi, Jiandong Liu, Li Qian
Myocardial infarction afflicts close to three quarters of a million Americans annually, resulting in reduced heart function, arrhythmia, and frequently death. Cardiomyocyte death reduces the heart's pump capacity while the deposition of a non-conductive scar incurs the risk of arrhythmia. Direct cardiac reprogramming emerged as a novel technology to simultaneously reduce scar tissue and generate new cardiomyocytes to restore cardiac function. This technology converts endogenous cardiac fibroblasts directly into induced cardiomyocyte-like cells using a variety of cocktails including transcription factors, microRNAs, and small molecules...
April 7, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28389561/tgf-beta-1-induced-cd44v6-nox4-signaling-in-pathogenesis-of-idiopathic-pulmonary-fibrosis
#13
Shibnath Ghatak, Vincent C Hascall, Roger R Markwald, Carol Feghali-Bostwick, Carol M Artlett, Monika Gooz, Galina S Bogatkevich, Ilia Atanelishvili, Richard M Silver, Jeanette Wood, Victor J Thannickal, Suniti Misra
Idiopathic pulmonary fibrosis (IPF) is a progressive clinical syndrome of fatal outcome. The lack of information about the signaling pathways that sustain fibrosis and the myofibroblasts phenotype has prevented the development of targeted therapies for IPF. Our previous study (1) showed that isolated fibrogenic lung fibroblasts have high endogenous levels of the hyaluronan receptor, CD44v6 (CD44-variants containing exon-6), which enhances the TGF-beta-1 autocrine signaling and induces fibroblasts to transdifferentiate into myofibroblasts...
April 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28382363/micropatterned-co-culture-of-cardiac-myocytes-on-fibrous-scaffolds-for-predictive-screening-of-drug-cardiotoxicities
#14
Yaowen Liu, Tian Xia, Jiaojun Wei, Qingjie Liu, Xiaohong Li
The spatial arrangement of cardiac myocytes (CMs) and other non-myocytes scaffolds, closely resembling native tissue, is essential to control the CM morphology and function for cardiac tissue regeneration. In the current study, micropatterned fibrous scaffolds were developed to establish a CM co-culture system with cardiac fibroblasts (CFs) and endothelial cells (ECs) as a potential in vitro drug screening model. To pursue a biomimetic approach to influence CM behaviors, strip, oval and wave-patterned mats were constructed by deposition of electrospun fibers on lithographic collectors, followed by precise stacking for cell co-cultures...
April 6, 2017: Nanoscale
https://www.readbyqxmd.com/read/28381471/sox17-regulates-conversion-of-human-fibroblasts-into-endothelial-cells-and-erythroblasts-via-de-differentiation-into-cd34-progenitor-cells
#15
Lianghui Zhang, Ankit Jambusaria, Zhigang Hong, Glenn Marsboom, Peter T Toth, Brittney-Shea Herbert, Asrar B Malik, Jalees Rehman
Background -The mechanisms underlying the de-differentiation and lineage conversion of adult human fibroblasts into functional endothelial cells have not yet been fully defined. Furthermore, it is not known whether fibroblast de-differentiation recapitulates the generation of multipotent progenitors during embryonic development which give rise to endothelial and hematopoietic cell lineages. Here we established the role of the developmental transcription factor SOX17 in regulating the bi-lineage conversion of fibroblasts via the generation of intermediate progenitors...
April 5, 2017: Circulation
https://www.readbyqxmd.com/read/28381466/intracellular-angiotensin-ii-interacts-with-nuclear-angiotensin-receptors-in-cardiac-fibroblasts-and-regulates-rna-synthesis-cell-proliferation-and-collagen-secretion
#16
Artavazd Tadevosyan, Jiening Xiao, Sirirat Surinkaew, Patrice Naud, Clémence Merlen, Masahide Harada, Xiaoyan Qi, David Chatenet, Alain Fournier, Bruce G Allen, Stanley Nattel
BACKGROUND: Cardiac fibroblasts play important functional and pathophysiological roles. Intracellular ("intracrine") angiotensin-II (Ang-II) signaling regulates intercellular communication, excitability, and gene expression in cardiomyocytes; however, the existence and role of intracrine Ang-II signaling in cardiac fibroblasts is unstudied. Here, we evaluated the localization of Ang-II receptors on atrial fibroblast nuclei and associated intracrine effects of potential functional significance...
April 5, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28378397/relationship-among-lrp1-expression-pyk2-phosphorylation-and-mmp-9-activation-in-left-ventricular-remodelling-after-myocardial-infarction
#17
Elena Revuelta-López, Carol Soler-Botija, Laura Nasarre, Aleyda Benitez-Amaro, David de Gonzalo-Calvo, Antoni Bayes-Genis, Vicenta Llorente-Cortés
Left ventricular (LV) remodelling after myocardial infarction (MI) is a crucial determinant of the clinical course of heart failure. Matrix metalloproteinase (MMP) activation is strongly associated with LV remodelling after MI. Elucidation of plasma membrane receptors related to the activation of specific MMPs is fundamental for treating adverse cardiac remodelling after MI. The aim of current investigation was to explore the potential association between the low-density lipoprotein receptor-related protein 1 (LRP1) and MMP-9 and MMP-2 spatiotemporal expression after MI...
April 4, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28378126/global-transcriptomic-analysis-of-induced-cardiomyocytes-predicts-novel-regulators-for-direct-cardiac-reprogramming
#18
Mahmood Talkhabi, Seyed Morteza Razavi, Ali Salari
Heart diseases are the most significant cause of morbidity and mortality in the world. De novo generated cardiomyocytes (CMs) are a great cellular source for cell-based therapy and other potential applications. Direct cardiac reprogramming is the newest method to produce CMs, known as induced cardiomyocytes (iCMs). During a direct cardiac reprogramming, also known as transdifferentiation, non-cardiac differentiated adult cells are reprogrammed to cardiac identity by forced expression of cardiac-specific transcription factors (TFs) or microRNAs...
April 4, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28377431/the-renal-and-cardiovascular-effects-of-natriuretic-peptides
#19
Philip Ching Yat Wong, Jun Guo, Aidong Zhang
The landmark report by de Bold et al. in 1981 signified the heart as one of the endocrine organs involved in fluid and salt balance (de Bold AJ, Borenstein HB, Veress AT, Sonnenberg H. Life Sci 28: 89-94, 1981). Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are secreted from cardiomyocytes in response to cardiac stretch as in the case of heart failure, whereas C-type natriuretic peptide (CNP) is secreted from endothelial and renal cells in response to cytokines and endothelium-dependent agonists, such as acetylcholine...
June 1, 2017: Advances in Physiology Education
https://www.readbyqxmd.com/read/28376483/long-non-coding-rnas-in-cardiac-remodeling
#20
Shutong Shen, Huimin Jiang, Yihua Bei, Junjie Xiao, Xinli Li
Cardiac remodeling occurs after stress to the heart, manifested as pathological processes, including hypertrophy and apoptosis of cardiomyocytes, dysfunction of vascular endothelial cells and vascular smooth muscle cells as well as differentiation and proliferation of fibroblasts, ultimately resulting in progression of cardiovascular diseases. Emerging evidence has revealed that long non-coding RNAs (lncRNAs) acted as powerful and dynamic modifiers of cardiac remodeling. LncRNAs including Chaer, Chast, Mhrt, CHRF, ROR, H19, and MIAT have been implicated in cardiac hypertrophy while NRF, H19, APF, CARL, UCA, Mhrt and several other lncRNAs (n379599, n379519, n384640, n380433 and n410105) in cardiomyocyte loss and extracellular matrix remodeling...
April 3, 2017: Cellular Physiology and Biochemistry
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