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Circulation Research

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https://www.readbyqxmd.com/read/28928113/pdk4-inhibits-cardiac-pyruvate-oxidation-in-late-pregnancy
#1
Laura 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
#2
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
#3
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/28923791/gja1-20k-arranges-actin-to-guide-cx43-delivery-to-cardiac-intercalated-discs
#4
Wassim A Basheer, Shaohua Xiao, Irina Epifantseva, Ying Fu, Andre G Kleber, TingTing Hong, Robin M Shaw
Rationale: Delivery of connexin 43 (Cx43) to the intercalated disc is a continuous and rapid process critical for intercellular coupling. By a pathway of targeted delivery involving microtubule highways, vesicles of Cx43 hemichannels are efficiently trafficked to adherens junctions at intercalated discs. It has also been identified that actin provides rest stops for Cx43 forward trafficking, and that Cx43 has a 20kDa internally translated small C-terminus isoform (GJA1-20k) which is required for full-length Cx43 trafficking, but by an unknown mechanism...
September 18, 2017: Circulation Research
https://www.readbyqxmd.com/read/28912121/cortical-bone-stem-cell-therapy-preserves-cardiac-structure-and-function-after-myocardial-infarction
#5
Thomas E Sharp, Giana J Schena, Alexander R Hoachlandr-Hobby, Timothy Starosta, Remus M Berretta, Markus Wallner, Giulia Borghetti, Polina Gross, Daohai Yu, Jaslyn Johnson, Eric A Feldsott, Danielle M Trappanese, Amir Toib, Joseph E Rabinowitz, Jon C George, Hajime Kubo, Sadia Mohsin, Steven R Houser
Rationale: Cortical bone stem cells (CBSCs) have been shown to reduce ventricular remodeling and improve cardiac function in a murine myocardial infarction (MI) model. These effects were superior to other stem cell types that have been used in recent early stage clinical trials. However, CBSC efficacy has not been tested in a preclinical large animal model using approaches that could be applied to patients. Objective: To determine if post-MI transendocardial injection of allogeneic CBSCs reduces pathological structural and functional remodeling and prevents the development of heart failure in a swine MI model...
September 14, 2017: Circulation Research
https://www.readbyqxmd.com/read/28874395/celf1-mediates-connexin-43-mrna-degradation-in-dilated-cardiomyopathy
#6
Kuei-Ting Chang, Ching-Feng Cheng, Pei-Chih King, Shin-Yi Liu, Guey-Shin Wang
Rationale: Downregulation of connexin 43 (Cx43), the major cardiac gap junction protein, is often associated with arrhythmia, dilated cardiomyopathy (DCM) and heart failure. However, the cause of the reduced expression remains elusive. Re-induction of a nuclear RNA-binding protein CUGBP, Elav-like family member 1 (CELF1) in the adult heart has been implicated in the cardiac pathogenesis of myotonic dystrophy type 1 (DM1). However, how elevated CELF1 level leads to cardiac dysfunction, such as conduction defect, DCM and heart failure, remains unclear...
September 5, 2017: Circulation Research
https://www.readbyqxmd.com/read/28855204/regulation-of-macrophage-apoptosis-and-atherosclerosis-by-lipid-induced-pkc%C3%AE-isoform-activation
#7
Qian Li, Kyoungmin Park, Yu Xia, Motonobu Matsumoto, Weier Qi, Jialin Fu, Hisashi Yokomizo, Mogher Khamaisi, Xuanchun Wang, Christian Rask-Madsen, George L King
Rationale: Activation of monocytes/macrophages by hyperlipidemia associated with diabetes and obesity contributes to the development of atherosclerosis. PKCδ expression and activity in monocytes were increased by hyperlipidemia and diabetes with unknown consequences to atherosclerosis. Objective: To investigate the effect of PKCδ activation in macrophages on the severity of atherosclerosis. Methods and Results: PKCδ expression and activity were increased in Zucker diabetic rats. Mice with selective deletion of PKCδ in macrophages were generated by breeding PKCδ flox/flox mice with LyzM-Cre and ApoE(-/-) mice (MPKCδKO/ApoE(-/-) mice) and studied in atherogenic (AD) and very high fat diet (HFD)...
August 30, 2017: Circulation Research
https://www.readbyqxmd.com/read/28851810/mertk-cleavage-on-resident-cardiac-macrophages-compromises-repair-after-myocardial-ischemia-reperfusion-injury
#8
Matthew DeBerge, Xin-Yi Yeap, Shirley Dehn, Shuang Zhang, Lubov S Grigoryeva, Sol Misener, Daniele Procissi, Xin Zhou, Daniel C Lee, William A Muller, Xunrong Luo, Carla Rothlin, Ira Tabas, Edward B Thorp
Rationale: Clinical benefits of reperfusion after myocardial infarction (MI) are offset by maladaptive innate immune cell function and therapeutic interventions are lacking. Objective: We sought to test the significance of phagocytic clearance by resident and recruited phagocytes after myocardial ischemia reperfusion (I/R). Methods and Results: In humans, we discovered that clinical reperfusion after MI led to significant elevation of the soluble form of MerTK (i.e. solMER), a critical biomarker of compromised phagocytosis by innate macrophages...
August 29, 2017: Circulation Research
https://www.readbyqxmd.com/read/28851809/postnatal-cardiac-gene-editing-using-crispr-cas9-with-aav9-mediated-delivery-of-short-guide-rnas-results-in-mosaic-gene-disruption
#9
Anne K Johansen, Bas Molenaar, Danielle Versteeg, Ana R Leitoguinho, Charlotte J Demkes, Bastiaan Spanjaard, Hesther de Ruiter, Farhad A Akbari Moqadam, Lieneke Kooijman, Lorena Zentilin, Mauro Giacca, Eva van Rooij
Rationale: CRISPR/Cas9-based DNA editing has rapidly evolved as an attractive tool to modify the genome. Although CRISPR/Cas9 has been extensively used to manipulate the germline in zygotes, its application in postnatal gene editing remains incompletely characterized. Objective: To evaluate the feasibility of CRISPR/Cas9-based cardiac genome editing in vivo in postnatal mice. Methods and Results: We generated cardiomyocyte-specific Cas9 mice and demonstrated that Cas9 expression does not affect cardiac function or gene expression...
August 29, 2017: Circulation Research
https://www.readbyqxmd.com/read/28835357/activation-of-%C3%AE-2-ampk-suppresses-ribosome-biogenesis-and-protects-against-myocardial-ischemia-reperfusion-injury
#10
Yang Cao, Naveen Bojjireddy, Maengjo Kim, Tao Li, Peiyong Zhai, Narayani Nagarajan, Junichi Sadoshima, Richard D Palmiter, Rong Tian
Rationale: AMP-activated protein kinase (AMPK) is a heterotrimeric protein that plays an important role in energy homeostasis and cardioprotection. Two isoforms of each subunit are expressed in the heart but the isoform-specific function of AMPK remains unclear. Objective: We sought to determine the role of γ2-AMPK in cardiac stress response using bioengineered cell lines and mouse models containing either isoform of the γ-subunit in the heart. Methods and Results: We found that γ2 but not γ1 or γ3 subunit translocated into nucleus upon AMPK activation...
August 23, 2017: Circulation Research
https://www.readbyqxmd.com/read/28827412/macrophage-liver-kinase-b1-inhibits-foam-cell-formation-and-atherosclerosis
#11
Zhaoyu Liu, Huaiping Zhu, Xaoyan Dai, Cheng Wang, Ye Ding, Ping Song, Ming-Hui Zou
Rationale: Liver kinase B1 (LKB1) is a serine/threonine kinase and tumor suppressor, which regulates the homeostasis of hematopoietic cells and immune responses. Macrophages transform into foam cells upon taking-in lipids. No role for LKB1 in foam cell formation has previously reported. Objective: We sought to establish the role of LKB1 in atherosclerotic foam cell formation. Methods and Results: LKB1 expression was examined in human carotid atherosclerotic plaques and in western diet fed atherosclerosis-prone Ldlr(-/-) and ApoE(-/-) mice...
August 21, 2017: Circulation Research
https://www.readbyqxmd.com/read/28821541/targeting-mir-423-5p-reverses-exercise-training-induced-hcn4-channel-remodeling-and-sinus-bradycardia
#12
Alicia D'Souza, Charles M Pearman, Yanwen Wang, Shu Nakao, Sunil Jit R Logantha, Charlotte Cox, Hayley J Bennett, Yu Zhang, Anne Berit Johnsen, Nora Linscheid, Pi C Poulsen, Jonathan Elliott, Jessica Coulson, Jamie S McPhee, Abigail C Robertson, Paula A da Costa Martins, Ashraf Kitmitto, Ulrik Wisloff, Elizabeth J Cartwright, Oliver Monfredi, Alicia Lundby, Halina Dobrzynski, Delvac Oceandy, Gwilym M Morris, Mark R Boyett
Rationale: Downregulation of the pacemaking ion channel, HCN4, and the corresponding ionic current, If, underlies exercise training-induced sinus bradycardia in rodents. If this occurs in humans, it could explain the increased incidence of bradyarrhythmias in veteran athletes and it will be important to understand the underlying processes. Objective: To test the role of HCN4 in the training-induced bradycardia in human athletes and investigate the role of micro-RNAs (miRs) in the repression of HCN4. Methods and Results: As in rodents, the intrinsic heart rate was significantly lower in human athletes than non-athletes and in all subjects the rate-lowering effect of the HCN selective blocker, ivabradine, was significantly correlated with the intrinsic heart rate, consistent with HCN repression in athletes...
August 17, 2017: Circulation Research
https://www.readbyqxmd.com/read/28794054/cardiovascular-event-prediction-by-machine-learning-the-multi-ethnic-study-of-atherosclerosis
#13
Bharath Ambale-Venkatesh, Xiaoying Yang, Colin O Wu, Kiang Liu, W G Hundley, Robyn L McClelland, Antoinette S Gomes, Aaron R Folsom, Steven Shea, Eliseo Guallar, David A Bluemke, João A Lima
Rationale: Machine learning may be useful to characterize cardiovascular risk, predict outcomes and identify biomarkers in population studies. Objective: To test the ability of random survival forests (RF), a machine learning technique, to predict six cardiovascular outcomes in comparison to standard cardiovascular risk scores. Methods and Results: We included participants from the Multi-Ethnic Study of Atherosclerosis (MESA). Baseline measurements were used to predict cardiovascular outcomes over 12 years of follow-up...
August 9, 2017: Circulation Research
https://www.readbyqxmd.com/read/28790199/in-vivo-genome-editing-restores-dystrophin-expression-and-cardiac-function-in-dystrophic-mice
#14
Mona El Refaey, Li Xu, Yandi Gao, Benjamin D Canan, Tm A Adesanya, Sarah C Warner, Keiko Akagi, David E Symer, Peter J Mohler, Jianjie Ma, Paul M Janssen, Renzhi Han
Rationale: Duchenne muscular dystrophy (DMD) is a severe inherited form of muscular dystrophy caused by mutations in the reading frame of the dystrophin gene disrupting its protein expression. Dystrophic cardiomyopathy is a leading cause of death in DMD patients and currently no effective treatment exists to halt its progression. Recent advancement in genome editing technologies offers a promising therapeutic approach in restoring dystrophin protein expression. However, the impact of this approach on DMD cardiac function has yet to be evaluated...
August 8, 2017: Circulation Research
https://www.readbyqxmd.com/read/28790198/neutrophil-activation-of-endothelial-cell-expressed-trpm2-mediates-transendothelial-neutrophil-migration-and-vascular-injury
#15
Manish Mittal, Saroj Nepal, Yoshikazu Tsukasaki, Claudie M Hecquet, Dheeraj Soni, Jalees Rehman, Chinnaswamy Tiruppathi, Asrar B Malik
Rationale: TRPM2 (Transient Receptor Potential Melastatin-2) expressed in endothelial cells (ECs) is a cation channel mediating Ca(2+) entry in response to intracellular generation of adenosine diphosphoribose (ADPR), the TRPM2 ligand. Objective: Because polymorphonuclear leukocytes (PMN) interaction with endothelial cells (ECs) generates ROS, we addressed the possible role of TRPM2 expressed in ECs in the mechanism of transendothelial migration of PMNs. Methods and Results: We observed defective PMN transmigration in response to LPS challenge in adult mice in which the EC expressed TRPM2 is conditionally deleted (Trpm2(iΔEC) )...
August 8, 2017: Circulation Research
https://www.readbyqxmd.com/read/28775078/tlr2-plays-a-key-role-in-platelet-hyperreactivity-and-accelerated-thrombosis-associated-with-hyperlipidemia
#16
Sudipta Biswas, Alejandro Zimman, Detao Gao, Tatiana Byzova, Eugene Podrez
Rationale: Platelet hyperreactivity, which is common in many pathological conditions, is associated with increased atherothrombotic risk. The mechanisms leading to platelet hyperreactivity are complex and not yet fully understood. Objective: Platelet hyperreactivity and accelerated thrombosis, specifically in dyslipidemia, have been mechanistically linked to accumulation in the circulation of a specific group of oxidized phospholipids (oxPCCD36) that are ligands for the platelet pattern-recognition receptor CD36...
August 3, 2017: Circulation Research
https://www.readbyqxmd.com/read/28739590/mast-cells-granular-contents-are-crucial-for-deep-vein-thrombosis-in-mice
#17
Tatyana Ponomaryov, Holly Payne, Larissa Fabritz, Denisa D Wagner, Alexander Brill
Rationale: Deep vein thrombosis (DVT) and its complication pulmonary embolism have high morbidity reducing quality of life and leading to death. Cellular mechanisms of DVT initiation remain poorly understood. Objective: We sought to determine the role of mast cells (MCs) in DVT initiation and validate MCs as a potential target for DVT prevention. Methods and Results: In a mouse model, DVT was induced by partial ligation (stenosis) of the inferior vena cava (IVC). We demonstrated that two strains of mice deficient for MCs were completely protected from DVT...
July 24, 2017: Circulation Research
https://www.readbyqxmd.com/read/28729354/continuous-flow-lvad-support-causes-a-distinct-form-of-intestinal-angiodysplasia
#18
Jooeun Kang, Samson Hennessy-Strahs, Pawel Kwiatkowski, Christian Bermudez, Michael A Acker, Pavan Atluri, Patrick McConnell, Carlo R Bartoli
Rationale: The objective of this autopsy study was to determine whether abnormal gastrointestinal vascularity develops during continuous-flow LVAD support. Objective: Left ventricular assist device (LVAD) support causes pathologic degradation of von Willebrand factor (vWF) and bleeding from gastrointestinal angiodysplasia at an alarming rate. It has been speculated that LVAD support, itself may cause angiodysplasia. The relationship to abnormal vWF metabolism is unknown. We tested the hypothesis that abnormal gastrointestinal vascularity develops during continuous-flow LVAD support...
July 20, 2017: Circulation Research
https://www.readbyqxmd.com/read/28724745/seq-identifies-circulating-mir-125a-5p-mir-125b-5p-and-mir-143-3p-as-potential-biomarkers-for-acute-ischemic-stroke
#19
Steffen Tiedt, Matthias Prestel, Rainer Malik, Nicola Schieferdecker, Marco Düring, Veronika Kautzky, Ivelina Stoycheva, Julia Böck, Bernd H Northoff, Matthias Klein, Franziska Dorn, Knut Krohn, Daniel Teupser, Arthur Liesz, Nikolaus Plesnila, Lesca M Holdt, Martin Dichgans
Rationale: Currently, there are no blood-based biomarkers with clinical utility for acute ischemic stroke (IS). microRNAs (miRNAs) show promise as disease markers due to their cell-type specific expression patterns and stability in peripheral blood. Objective: To identify circulating miRNAs associated with acute IS, determine their temporal course up to 90 days post-stroke, and explore their utility as an early diagnostic marker. Methods and Results: We used RNA sequencing to study expression changes of circulating miRNAs in a discovery sample of 20 IS patients and 20 matched healthy control subjects (HCs)...
July 19, 2017: Circulation Research
https://www.readbyqxmd.com/read/28912188/modern-imaging-techniques-in-cardiomyopathies
#20
REVIEW
M Fuad Jan, A Jamil Tajik
Modern advanced imaging techniques have allowed increasingly more rigorous assessment of the cardiac structure and function of several types of cardiomyopathies. In contemporary cardiology practice, echocardiography and cardiac magnetic resonance imaging are widely used to provide a basic framework in the evaluation and management of cardiomyopathies. Echocardiography is the quintessential imaging technique owing to its unique ability to provide real-time images of the beating heart with good temporal resolution, combined with its noninvasive nature, cost-effectiveness, availability, and portability...
September 15, 2017: Circulation Research
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