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Circulation Research

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https://www.readbyqxmd.com/read/29158345/stable-oxidative-cytosine-modifications-accumulate-in-cardiac-mesenchymal-cells-from-type2-diabetes-patients-rescue-by-alpha-ketoglutarate-and-tet-tdg-functional-reactivation
#1
Francesco Spallotta, Chiara Cencioni, Sandra Atlante, Davide Garella, Mattia Cocco, Mattia Mori, Raffaella Mastrocola, Carsten Künne, Stefan Günther, Simona Nanni, Valerio Azzimato, Sven Zukunft, Angela Kornberger, Duran Sueruen, Frank Schnutgen, Harald von Melchner, Antonella Di Stilo, Manuela Aragno, Maarten Braspenning, Wim Van Criekinge, Miles J De Blasio, Rebecca H Ritchie, Germana Zaccagnini, Fabio Martelli, Antonella Farsetti, Ingrid Fleming, Thomas Braun, Andres Beiras-Fernandez, Bruno Botta, Massimo Collino, Massimo Bertinaria, Andreas M Zeiher, Carlo Gaetano
Rationale: Human cardiac mesenchymal cells (CMSCs) are a therapeutically-relevant primary cell population. Diabetes compromises CMSC function as consequence of metabolic alterations and incorporation of stable epigenetic changes. Objective: To investigate the role of α-ketoglutarate (αKG) in the epi-metabolic control of DNA demethylation in CMSCs. Methods and Results: Quantitative global analysis, methylated and hydroxymethylated DNA sequencing and gene specific GC methylation detection revealed an accumulation of 5mC, 5hmC and 5fC in the genomic DNA of human CMSCs isolated from diabetic (D) donors (D-CMSCs)...
November 20, 2017: Circulation Research
https://www.readbyqxmd.com/read/29133306/quaking-inhibits-doxorubicin-mediated-cardiotoxicity-through-regulation-of-cardiac-circular-rna-expression
#2
Shashi K Gupta, Ankita Garg, Christian Bär, Shambhabi Chatterjee, Ariana Foinquinos, Hendrik Milting, Katrin Streckfuss-Bömeke, Jan Fiedler, Thomas Thum
Rationale: RNA-binding proteins (RBPs) have been described to be expressed and regulated in various organs including the heart. Little is known about the role of RBPs in heart failure induced by the chemotherapy drug doxorubicin and their interaction with circular RNAs. Objective: We aimed to identify key RBPs involved in doxorubicin-mediated heart failure and to elucidate their function. Methods and Results: Global transcriptome profiling from murine myocardium exposed to doxorubicin identified five differentially expressed RBPs...
November 13, 2017: Circulation Research
https://www.readbyqxmd.com/read/29118058/induced-pluripotent-stem-cell-ipsc-derived-extracellular-vesicles-are-safer-and-more-effective-for-cardiac-repair-than-ipscs
#3
Marta Adamiak, Guangming Cheng, Sylwia Bobis-Wozowicz, Lin Zhao, Sylwia Kedracka-Krok, Anweshan Samanta, Elzbieta Karnas, Yu-Ting Xuan, Bozena Skupien-Rabian, Xing Chen, Urszula Jankowska, Magdy Girgis, Malgorzata Sekula, Arash Davani, Slawomir Lasota, Robert J Vincent, Michal Sarna, Kathy L Newell, Ou-Li Wang, Nathaniel Dudley, Zbigniew Madeja, Buddhadeb Dawn, Ewa K Zuba-Surma
Rationale: Extracellular vesicles (EVs) are tiny membrane-enclosed droplets released by cells through membrane budding or exocytosis. The myocardial reparative abilities of EVs derived from induced pluripotent stem cells (iPSCs) have not been directly compared with the source iPSCs. Objective: To examine whether iPSC-derived EVs can influence the biological functions of cardiac cells in vitro; and compare the safety and efficacy of iPSC-EVs and iPSCs for cardiac repair in vivo. Methods and Results: Murine iPSCs were generated and EVs isolated from culture supernatants by sequential centrifugation...
November 8, 2017: Circulation Research
https://www.readbyqxmd.com/read/29113965/mitochondrial-oxidative-stress-reduces-the-immunopotency-of-mesenchymal-stromal-cells-in-adults-with-coronary-artery-disease
#4
Ozge Kizilay Mancini, Maximilien Lora, Alexanne Cuillerier, Dominique Shum-Tim, Reggie C Hamdy, Yan Burelle, Marc J Servant, Ursula Stochaj, Ines Colmegna
Rationale: Mesenchymal stromal cells (MSCs) are promising therapeutic strategies for coronary artery disease (CAD), however, donor-related variability in cell quality is a main cause of discrepancies in preclinical studies. In vitro, MSCs from individuals with CAD have reduced ability to suppress activated T-cells. The mechanisms underlying the altered immunomodulatory capacity of MSCs in the context of atherosclerosis (ATH) remain elusive. Objective: The aim of this study was to assess the role of mitochondrial dysfunction in the impaired immunomodulatory properties of MSCs from ATH patients...
November 7, 2017: Circulation Research
https://www.readbyqxmd.com/read/29097437/associations-of-endogenous-estradiol-and-testosterone-levels-with-plaque-composition-and-risk-of-stroke-in-subjects-with-carotid-atherosclerosis
#5
Marija Glisic, Blerim Mujaj, Oscar L Rueda-Ochoa, Eralda Asllanaj, Joop S Laven, Maryam Kavousi, M Kamran Ikram, Meike W Vernooij, M Arfan Ikram, Oscar H Franco, Daniel Bos, Taulant Muka
Rationale: Sex steroids may play a role in plaque composition and in stroke incidence. Objective: To study the associations of endogenous estradiol and testosterone with carotid plaque composition in elderly men and postmenopausal women with carotid atherosclerosis, as well as with risk of stroke in this population. Methods and Results: Data of 1023 postmenopausal women and 1124 men (≥45 years) with carotid atherosclerosis, from prospective population-based Rotterdam Study, were available. At baseline, total estradiol (TE) and total testosterone (TT) were measured...
November 2, 2017: Circulation Research
https://www.readbyqxmd.com/read/29092894/mitochondrial-reactive-oxygen-species-in-lipotoxic-hearts-induces-post-translational-modifications-of-akap121-drp1-and-opa1-that-promote-mitochondrial-fission
#6
Kensuke Tsushima, Heiko Bugger, Adam R Wende, Jamie Soto, Gregory A Jenson, Austin R Tor, Rose McGlauflin, Helena C Kenny, Yuan Zhang, Rhonda Souvenir, Xiao X Hu, Crystal L Black, Renata O Pereira, Vitor A Lira, Kenneth Spitzer, Terry L Sharp, Kooresh I Shoghi, Genevieve C Sparagna, Eva A Rog-Zielinska, Peter Kohl, Oleh Khalimonchuk, Jean E Schaffer, E Dale Abel
Rationale: Cardiac lipotoxicity, characterized by increased uptake, oxidation and accumulation of lipid intermediates, contributes to cardiac dysfunction in obesity and diabetes. However, mechanisms linking lipid overload and mitochondrial dysfunction are incompletely understood. Objective: To elucidate the mechanisms for mitochondrial adaptations to lipid overload in postnatal hearts in vivo. Methods and Results: Using a transgenic mouse model of cardiac lipotoxicity overexpressing long-chain acyl-CoA synthetase 1 in cardiomyocytes, we show that modestly increased myocardial fatty acid uptake leads to mitochondrial structural remodeling with significant reduction in minimum diameter...
November 1, 2017: Circulation Research
https://www.readbyqxmd.com/read/29089350/unspliced-xbp1-confers-vsmc-homeostasis-and-prevents-aortic-aneurysm-formation-via-foxo4-interaction
#7
Guizhen Zhao, Yi Fu, Zeyu Cai, Fang Yu, Ze Gong, Rongbo Dai, Yanhua Hu, Lingfang Zeng, Qingbo Xu, Wei Kong
Rationale: Although not fully understood, the phenotypic transition of vascular smooth muscle cells exhibits at the early onset of the pathology of aortic aneurysms. Exploring the key regulators that are responsible for maintaining the contractile phenotype of VSMCs may confer vascular homeostasis and prevent aneurysmal disease. X-box binding protein 1, which exists in a transcriptionally inactive unspliced form (XBP1u) and a spliced active form (XBP1s), is a key component in response to endoplasmic reticular (ER) stress...
October 31, 2017: Circulation Research
https://www.readbyqxmd.com/read/29089349/thyroid-function-and-the-risk-of-atherosclerotic-cardiovascular-morbidity-and-mortality-the-rotterdam-study
#8
Arjola Bano, Layal Chaker, Francesco U Mattace-Raso, Aad van der Lugt, M Arfan Ikram, Oscar H Franco, Robin P Peeters, Maryam Kavousi
Rationale: Thyroid hormones have been linked with various proatherogenic and antiatherogenic processes. However, the relationship of thyroid function with manifestations of atherosclerosis remains unclear. Objective: To investigate the association of thyroid function with atherosclerosis throughout its spectrum; i.e. subclinical atherosclerosis, incident atherosclerotic cardiovascular (ASCV) events and ASCV mortality. Methods and Results: This population-based study was embedded within the Rotterdam Study. The risk of atherosclerosis was evaluated by measuring: 1...
October 31, 2017: Circulation Research
https://www.readbyqxmd.com/read/29051340/attenuation-of-myeloid-specific-tgf%C3%AE-signaling-induces-inflammatory-cerebrovascular-disease-and-stroke
#9
M C Hollander, Lawrence L Latour, Dan Yang, Hiroki Ishii, Zhiguang Xiao, Yongfen Min, Abhik Ray-Choudhury, Jeeva Munasinghe, Anand S Merchant, P C Lin, John Hallenbeck, Manfred Boehm, Li Yang
Rationale: Cryptogenic strokes, those of unknown cause, have been estimated as high as 30-40% of strokes. Inflammation has been suggested as a critical etiological factor. However, there is lack of experimental evidence. Objective: In this study, we investigated inflammation associated stroke etiology using a mouse model that developed spontaneous stroke due to myeloid deficiency of TGFβ signaling. Methods and Results: We report that mice with deletion of Tgfbr2 in myeloid cells (Tgfbr2(Myeko)) developed cerebrovascular inflammation in the absence of significant pathology in other tissues, culminating in stroke and severe neurological deficits with 100% penetrance...
October 19, 2017: Circulation Research
https://www.readbyqxmd.com/read/29046274/genetic-depletion-or-hyperresponsiveness-of-natural-killer-cells-do-not-affect-atherosclerosis-development
#10
Wared Nour-Eldine, Jeremie Joffre, Kazem Zibara, Andreas Giraud, Bruno Esposito, Lynda Zeboudj, José Vilar, Megumi Terada, Patrick Bruneval, Eric Vivier, Hafid Ait-Oufella, Ziad Mallat, Sophie Ugolini, Alain Tedgui
Rationale: Chronic inflammation is central in the development of atherosclerosis. Both innate and adaptive immunity are involved. Although several studies have evaluated the functions of NK cells in experimental animal models of atherosclerosis, it is not yet clear whether NK cells behave as protective or pro-atherogenic effectors. One of the main caveats of previous studies was the lack of specificity in targeting loss- or gain-of-function of NK cells. Objective: We used two selective genetic approaches to investigate the role of NK cells in atherosclerosis: 1) Ncr1i(Cre/+)R26(lsl-DTA/+) mice in which NK cells were depleted, 2) Noé mice in which NK cells are hyperresponsive...
October 18, 2017: Circulation Research
https://www.readbyqxmd.com/read/29021295/mitochondrial-cardiomyopathy-caused-by-elevated-reactive-oxygen-species-and-impaired-cardiomyocyte-proliferation
#11
Donghui Zhang, Yifei Li, Danielle A Heims-Waldron, Vassilios J Bezzerides, Silvia Guatimosim, Yuxuan Guo, Fei Gu, Pingzhu Zhou, Zhiqiang Lin, Qing Ma, Jianming Liu, Da-Zhi Wang, William T Pu
Rationale: Although mitochondrial diseases often cause abnormal myocardial development, the mechanisms by which mitochondria influence heart growth and function are poorly understood. Objective: To investigate these disease mechanisms, we studied a genetic model of mitochondrial dysfunction caused by inactivation of Tfam (Transcription Factor A, Mitochondrial), a nuclear-encoded gene that is essential for mitochondrial gene transcription and mitochondrial DNA replication. Methods and Results:Tfam inactivation by Nkx2...
October 11, 2017: Circulation Research
https://www.readbyqxmd.com/read/29018036/ccnd2-overexpression-enhances-the-regenerative-potency-of-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-remuscularization-of-injured-ventricle
#12
Wuqiang Zhu, Meng Zhao, Saidulu Mattapally, Sifeng Chen, Jianyi Zhang
Rationale: The effectiveness of transplanted, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for treatment of ischemic myocardial injury is limited by the exceptionally low engraftment rate. Objective: To determine whether overexpression of the cell-cycle activator CCND2 in hiPSC-CMs can increase the graft size and improve myocardial recovery in a mouse model of myocardial infarction (MI) by increasing the proliferation of grafted cells. Methods and Results: Human CCND2 was delivered to hiPSCs via lenti-viral mediated gene transfection...
October 10, 2017: Circulation Research
https://www.readbyqxmd.com/read/29018035/the-trials-and-tribulations-of-cetp-inhibitors
#13
Alan R Tall, Daniel J Rader
The development of CETP inhibitors has had a long and difficult course with three compounds failing in phase III clinical trials. Finally, the REVEAL trial has shown that the CETP inhibitor anacetrapib decreased coronary heart disease when added to statin therapy. While the result is different to earlier studies, this is likely related to the size and duration of the trial. The benefit of anacetrapib appears to be largely explained by lowering of non-HDL cholesterol, rather than increases in HDL cholesterol...
October 10, 2017: Circulation Research
https://www.readbyqxmd.com/read/29018034/a-distinct-cellular-basis-for-early-cardiac-arrhythmias-the-cardinal-manifestation-of-arrhythmogenic-cardiomyopathy-and-the-skin-phenotype-of-cardiocutaneous-syndromes
#14
Jennifer Karmouch, Qiong Q Zhou, Christina Y Miyake, Raffaella Lombardi, Kai Kretzschmar, Marie Bannier-Hélaouët, Hans Clevers, Xander H Wehrens, James T Willerson, Ali J Marian
Rationale: Arrhythmogenic cardiomyopathy (ACM) is caused primarily by mutations in genes encoding desmosome proteins. Ventricular arrhythmias are the cardinal and typically early manifestations, whereas myocardial fibroadiposis is the pathological hallmark. Homozygous DSP (desmoplakin) and JUP (plakoglobin) mutations are responsible for a subset of ACM patients that exhibit cardiac arrhythmias and dysfunction, palmo-planter keratosis, and hair abnormalities (cardiocutaneous syndromes). Objective: To determine phenotypic consequences of deletion of Dsp in a subset of cells common to the heart and skin...
October 10, 2017: Circulation Research
https://www.readbyqxmd.com/read/28974554/thyroid-and-glucocorticoid-hormones-promote-functional-t-tubule-development-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#15
Shan S Parikh, Daniel J Blackwell, Nieves Gomez-Hurtado, Michael Frisk, Lili Wang, Kyungsoo Kim, Christen P Dahl, Arnt E Fiane, Theis Tønnessen, Dmytro O Kryshtal, William E Louch, Bjorn C Knollmann
Rationale: Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CM) are increasingly being used for modeling heart disease and are under development for regeneration of the injured heart. However, incomplete structural and functional maturation of hiPSC-CM including lack of t-tubules, immature excitation-contraction (EC) coupling, and inefficient Ca-induced Ca release (CICR) remain major limitations. Objective: Thyroid and glucocorticoid hormones are critical for heart maturation. We hypothesized that their addition to standard protocols would promote t-tubule development and mature EC coupling of hiPSC-CM when cultured on extracellular matrix with physiological stiffness (Matrigel mattress)...
October 2, 2017: Circulation Research
https://www.readbyqxmd.com/read/28970285/calcium-dependent-arrhythmogenic-foci-created-by-weakly-coupled-myocytes-in-the-failing-heart
#16
Di Lang, Daisuke Sato, Yan Jiang, Kenneth S Ginsburg, Crystal M Ripplinger, Donald M Bers
Rationale: Intercellular uncoupling and Ca mishandling can initiate triggered ventricular arrhythmias. Spontaneous Ca release activates inward current which depolarizes membrane potential (Vm) and can trigger action potentials in isolated myocytes. However, cell-cell coupling in intact hearts limits local depolarization and may protect hearts from this arrhythmogenic mechanism. Traditional optical mapping lacks the spatial resolution to assess coupling of individual myocytes. Objective: We investigate local intercellular coupling in Ca-induced depolarization in intact hearts, using confocal microscopy to measure local Vm and intracellular [Ca(2+)] ([Ca]i) simultaneously...
October 2, 2017: Circulation Research
https://www.readbyqxmd.com/read/28928113/pdk4-inhibits-cardiac-pyruvate-oxidation-in-late-pregnancy
#17
Laura X Liu, Glenn C Rowe, Steven Yang, Jian Li, Federico Damilano, Mun Chun Chan, Wenyun Lu, Cholsoon Jang, Shogo Wada, Michael Morley, Michael Hesse, Bernd K Fleischmann, Joshua Rabinowitz, Saumya Das, Anthony Rosenzweig, Zoltan Arany
Rationale: Pregnancy profoundly alters maternal physiology. The heart hypertrophies during pregnancy, but its metabolic adaptations are not well understood. Objective: To determine the mechanisms underlying cardiac substrate use during pregnancy. Methods and Results: We use here (13)C-glucose, (13)C-lactate, and (13)C-fatty acid tracing analyses to show that hearts in late pregnant mice increase fatty acid uptake and oxidation into the tricarboxylic acid (TCA) cycle, while reducing glucose and lactate oxidation...
September 19, 2017: Circulation Research
https://www.readbyqxmd.com/read/28923793/dose-comparison-study-of-allogeneic-mesenchymal-stem-cells-in-patients-with-ischemic-cardiomyopathy-the-trident-study
#18
Victoria Florea, Angela C Rieger, Darcy L Difede, Jill El-Khorazaty, Makoto Natsumeda, Monisha N Banerjee, Bryon A Tompkins, Aisha Khan, Ivonne H Schulman, Ana M Landin, Muzammil Mushtaq, Maureen H Lowery, John Byrnes, Robert C Hendel, Mauricio G Cohen, Krystalenia Valasaki, Marietsy V Pujol, Eduard Ghersin, Roberto Miki, Cindy Delgado, Fouad A Abuzeid, Mayra Vidro-Casiano, Russell Saltzman, Daniel DaFonseca, Lina V Caceres, Kevin N Ramdas, Adam Mendizabal, Alan W Heldman, Raul D Mitrani, Joshua M Hare
Rationale: Cell dose and concentration play crucial roles in phenotypic responses to cell-based therapy for heart failure. Objective: To compare the safety and efficacy of two doses of allogeneic bone marrow-derived human mesenchymal stem cells (hMSC) identically delivered in patients with ischemic cardiomyopathy (ICM). Methods and Results: Thirty patients with ICM received in a blinded manner either 20 million (20M, n=15) or 100 million (100M, n=15) allogeneic hMSCs via transendocardial injection (10 0.5 cc injections/patient)...
September 18, 2017: Circulation Research
https://www.readbyqxmd.com/read/28923792/p2y2-nucleotide-receptor-prompts-human-cardiac-progenitor-cell-activation-by-modulating-hippo-signaling
#19
Farid G Khalafalla, Steven R Greene, Hashim Khan, Kelli Ilves, Megan M Monsanto, Roberto Alvarez, Monica Chavarria, Jonathan H Nguyen, Benjamin Norman, Walter P Dembitsky, Mark A Sussman
Rationale: Autologous stem cell therapy using human c-Kit(+) cardiac progenitor cells (hCPCs) is a promising therapeutic approach for treatment of heart failure (HF). However, hCPCs derived from aged HF patients with genetic predispositions and/or comorbidities of chronic diseases exhibit poor proliferative and migratory capabilities, which impairs overall reparative potential for injured myocardium. Therefore, empowering functionally compromised hCPCs with pro-regenerative molecules ex vivo is crucial for improving the therapeutic outcome in HF patients...
September 18, 2017: Circulation Research
https://www.readbyqxmd.com/read/29122946/correction-to-association-of-plasma-7-ketocholesterol-with-cardiovascular-outcomes-and-total-mortality-in-patients-with-coronary-artery-disease
#20
(no author information available yet)
No abstract text is available yet for this article.
November 10, 2017: Circulation Research
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