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Circulation Research

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https://www.readbyqxmd.com/read/28533209/rationale-and-design-of-a-clinical-trial-to-evaluate-the-safety-and-efficacy-of-intracoronary-infusion-of-allogeneic-human-cardiac-stem-cells-in-patients-with-acute-myocardial-infarction-and-left-ventricular-dysfunction-the-randomized-multicenter-double-blind
#1
Ricardo Sanz-Ruiz, Ana Casado Plasencia, Luis R Borlado, María Eugenia Fernández-Santos, Reem Al-Daccak, Piet Claus, Itziar Palacios, Rafael Sádaba, Dominique Charron, Jan Bogaert, Miguel Mulet, Raquel Yotti, Inmaculada Gilaberte, Antonio Bernad, Javier Bermejo, Stefan Janssens, Francisco Fernández-Avilés
Rationale: Stem cell therapy has increased the therapeutic armamentarium in the fight against ischemic heart disease and heart failure (HF). The administration of exogenous stem cells has been investigated in patients suffering an acute myocardial infarction (AMI) with the final aim of salvaging jeopardized myocardium and preventing left ventricular adverse remodeling and functional deterioration. However, phase I and II clinical trials with autologous and "first-generation" stem cells have yielded inconsistent benefits and mixed results...
May 22, 2017: Circulation Research
https://www.readbyqxmd.com/read/28522438/anti-inflammatory-effects-of-oxpapc-involve-endothelial-cell-mediated-generation-of-lxa4
#2
Yunbo Ke, Noureddine Zebda, Olga Oskokova, Taras Afonyushkin, Evgeny Berdyshev, Yufeng Tian, Fanyong Meng, Nicolene Sarich, Valery N Bochkov, Ji Ming Wang, Anna A Birukova, Konstantin G Birukov
Rationale: Oxidation of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine generates a group of bioactive oxidized phospholipid products (OxPAPC) with a broad range of biological activities. Barrier-enhancing and anti-inflammatory effects of OxPAPC on pulmonary endothelial cells (EC) are critical for prevention of acute lung injury caused by bacterial pathogens or excessive mechanical ventilation. Anti-inflammatory properties of OxPAPC are associated with its antagonistic effects on toll-like receptors and suppression of RhoA GTPase signaling...
May 18, 2017: Circulation Research
https://www.readbyqxmd.com/read/28515044/exploring-the-causal-pathway-from-telomere-length-to-coronary-heart-disease-a-network-mendelian-randomization-study
#3
Yiqiang Zhan, Ida K Karlsson, Robert Karlsson, Annika Tillander, Chandra A Reynolds, Nancy L Pedersen, Sara Hägg
Rationale: Observational studies have found shorter leukocyte telomere length to be a risk factor for coronary heart disease (CHD), and more recently the association was suggested to be causal. However, the relationship between telomere length and common metabolic risk factors for CHD is not well understood. Whether these risk factors could explain pathways from telomere length to CHD warrants further attention. Objective: To examine if metabolic risk factors for CHD mediate the causal pathway from short telomere length to increased risk of CHD using a network Mendelian randomization (MR) design...
May 17, 2017: Circulation Research
https://www.readbyqxmd.com/read/28515043/brain-perivascular-macrophages-initiate-the-neurovascular-dysfunction-of-alzheimer-a%C3%AE-peptides
#4
Laibaik Park, Ken Uekawa, Lidia Garcia-Bonilla, Kenzo Koizumi, Michelle Murphy, Rose Pitstick, Linda H Younkin, Steven G Younkin, Ping Zhou, Geroge A Carlson, Josef Anrather, Costantino Iadecola
Rationale: Increasing evidence indicates that alterations of the cerebral microcirculation may play a role in Alzheimer's disease (AD), the leading cause of late-life dementia. The amyloid-β peptide (Aβ), a key pathogenic factor in AD, induces profound alterations in neurovascular regulation through the innate immunity receptor CD36, which, in turn, activates a Nox2-containing NADPH oxidase leading to cerebrovascular oxidative stress. Brain perivascular macrophages (PVM) located in the perivascular space, a major site of brain Aβ collection and clearance, are juxtaposed to the wall of intracerebral resistance vessels and are a powerful source of reactive oxygen species (ROS)...
May 17, 2017: Circulation Research
https://www.readbyqxmd.com/read/28512108/clinical-relevance-and-role-of-neuronal-at1-receptors-in-adam17-mediated-ace2-shedding-in-neurogenic-hypertension
#5
Jiaxi Xu, Srinivas Sriramula, Huijing Xia, Lisa Moreno-Walton, Frank Culicchia, Oliver Domenig, Marko Poglitsch, Eric Lazartigues
Rationale: Neurogenic hypertension is characterized by an increase in sympathetic activity and often resistance to drug treatments. We previously reported that it is also associated with a reduction of Angiotensin Converting Enzyme 2 (ACE2) and an increase in A Disintegrin And Metalloprotease 17 (ADAM17) activity in experimental hypertension. In addition, while multiple cells within the central nervous system have been involved in the development of neurogenic hypertension, the contribution of ADAM17 has not been investigated...
May 16, 2017: Circulation Research
https://www.readbyqxmd.com/read/28512107/divergent-requirements-for-ezh1-in-heart-development-versus-regeneration
#6
Shanshan Ai, Xianhong Yu, Yumei Li, Yong Peng, Chen Li, Yanzhu Yue, Ge Tao, Chuan-Yun Li, William T Pu, Aibin He
Rationale: Polycomb repressive complex 2 (PRC2) is a major epigenetic repressor that deposits methylation on histone H3 on lysine 27 (H3K27me) and controls differentiation and function of many cells, including cardiac myocytes. EZH1 and EZH2 are two alternative catalytic subunits with partial functional redundancy. The relative roles of EZH1 and EZH2 in heart development and regeneration are unknown. Objective: We compared the roles of EZH1 versus EZH2 in heart development and neonatal heart regeneration. Methods and Results: Heart development was normal in Ezh1(-/-) (E1KO) and Ezh2(f/f)::cTNT(-Cre) (E2KO) embryos...
May 16, 2017: Circulation Research
https://www.readbyqxmd.com/read/28506971/protein-truncating-variants-at-the-cholesteryl-ester-transfer-protein-gene-and-risk-for-coronary-heart-disease
#7
Akihiro Nomura, Hong-Hee Won, Amit V Khera, Fumihiko Takeuchi, Kaoru Ito, Shane McCarthy, Connor A Emdin, Derek Klarin, Pradeep Natarajan, Seyedeh M Zekavat, Namrata Gupta, Gina M Peloso, Ingrid B Borecki, Tanya M Teslovich, Rosanna Asselta, Stefano Duga, Piera A Merlini, Adolfo Correa, Thorsten Kessler, James G Wilson, Matthew J Bown, Alistair S Hall, Peter S Braund, David J Carey, Michael F Murray, H L Kirchner, Joseph B Leader, Daniel R Lavage, J N Manus, Dustin N Hartzel, Nilesh J Samani, Heribert Schunkert, Jaume Marrugat, Roberto Elosua, Ruth McPherson, Martin Farrall, Hugh Watkins, Jyh-Ming Jimmy Juang, Chao A Hsiung, Shih-Yi Lin, Jun-Sing Wang, Hayato Tada, Masa-Aki Kawashiri, Akihiro Inazu, Masakazu Yamagishi, Tomohiro Katsuya, Eitaro Nakashima, Masahiro Nakatochi, Ken Yamamoto, Mitsuhiro Yokota, Yukihide Momozawa, Jerome I Rotter, Eric S Lander, Daniel J Rader, John N Danesh, Diego Ardissino, Stacey B Gabriel, Cristen J Willer, Gonçalo Abecasis, Danish Saleheen, Michiaki Kubo, Norihiro Kato, Yii-Der I Chen, Frederick Dewey, Sekar Kathiresan
Rationale: Therapies which inhibit cholesteryl ester transfer protein (CETP) have failed to demonstrate a reduction in risk for coronary heart disease (CHD). Human deoxyribonucleic acid sequence variants that truncate the CETP gene may provide insight into the efficacy of CETP inhibition. Objective: To test whether protein truncating variants (PTVs) at the CETP gene were associated with plasma lipid levels and CHD. Methods and Results: We sequenced the exons of the CETP gene in 58,469 participants from 12 case-control studies (18,817 CHD cases, 39,652 CHD-free controls)...
May 15, 2017: Circulation Research
https://www.readbyqxmd.com/read/28490433/peripheral-blood-cytokine-levels-after-acute-myocardial-infarction-il-1%C3%AE-and-il-6-related-impairment-of-bone-marrow-function
#8
Mahan Shahrivari, Elizabeth Wise, Micheline M Resende, Jonathan J Shuster, Jingnan Zhang, Roberto Bolli, John P Cooke, Joshua M Hare, Timothy D Henry, Aisha Khan, Doris A Taylor, Jay H Traverse, Phillip C Yang, Carl J Pepine, Christopher R Cogle
Rationale: Intracoronary infusion of bone marrow mononuclear cells (BM-MNCs) after acute myocardial infarction (AMI) has led to limited improvement in left ventricular (LV) function. Although experimental AMI models have implicated cytokine-related impairment of progenitor cell function, this response has not been investigated in humans. Objective: To test the hypothesis that peripheral blood (PB) cytokines predict bone marrow (BM) endothelial progenitor cell (EPC) colony outgrowth and cardiac function after AMI...
May 10, 2017: Circulation Research
https://www.readbyqxmd.com/read/28461455/loss-of-smooth-muscle-%C3%AE-actin-leads-to-nf-%C3%AE%C2%BAb-dependent-increased-sensitivity-to-angiontensin-ii-in-smooth-muscle-cells-and-aortic-enlargement
#9
Jiyuan Chen, Andrew M Peters, Christina L Papke, Carlos Villamizar, Lea-Jeanne Ringuette, Jiu-Mei Cao, Shanzhi Wang, Shuangtao Ma, Limin Gong, Katerina Byanova, Jian Xiong, Michael X Zhu, Rosalinda Madonna, Patrick Kee, Yong-Jian Geng, Allan Brasier, Elaine C Davis, Siddharth K Prakash, Callie S Kwartler, Dianna M Milewicz
Rationale: Mutations in ACTA2, encoding the smooth muscle isoform of α-actin (SM α-actin), cause thoracic aortic aneurysms, acute aortic dissections, and occlusive vascular diseases. Objective: We sought to identify the mechanism by which loss of SM α-actin causes aortic disease. Methods and Results:Acta2(-/-) mice have an increased number of elastic lamellae in the ascending aorta and progressive aortic root dilation as assessed by echocardiography that can be attenuated by treatment with losartan, an angiotensin II (AngII) type 1 receptor blocker...
May 1, 2017: Circulation Research
https://www.readbyqxmd.com/read/28446444/concurrent-isolation-of-three-distinct-cardiac-stem-cell-populations-from-a-single-human-heart-biopsy
#10
Megan M Monsanto, Kevin S White, Taeyong Kim, Bingyan J Wang, Kristina Fisher, Kelli Ilves, Farid G Khalafalla, Alexandria Casillas, Kathleen Broughton, Sadia Mohsin, Walter P Dembitsky, Mark A Sussman
Rationale: The relative actions and synergism between distinct myocardial-derived stem cell populations remains obscure. Ongoing debates regarding optimal cell population(s) for treatment of heart failure prompted implementation of a protocol for isolation of multiple stem cell populations from a single myocardial tissue sample to develop new insights for achieving myocardial regeneration. Objective: Establish a robust cardiac stem cell isolation and culture protocol to consistently generate three distinct stem cell populations from a single human heart biopsy...
April 26, 2017: Circulation Research
https://www.readbyqxmd.com/read/28438779/human-alternative-macrophages-populate-calcified-areas-of-atherosclerotic-lesions-and-display-impaired-rankl-induced-osteoclastic-bone-resorption-activity
#11
Giulia Chinetti-Gbaguidi, Mehdi Daoudi, Mickael Rosa, Manjula Vinod, Loïc Louvet, Corinne Copin, Melanie Fanchon, Jonathan Vanhoutte, Bruno Derudas, Loic Belloy, Stephan Haulon, Christophe Zawadzki, Sophie Susen, Ziad A Massy, Jérôme Eeckhoute, Bart Staels
Rationale: Vascular calcification is a process similar to bone formation leading to an inappropriate deposition of calcium phosphate minerals in advanced atherosclerotic plaques. Monocyte-derived macrophages, located in atherosclerotic lesions and presenting heterogeneous phenotypes, from classical pro-inflammatory M1 to alternative anti-inflammatory M2 macrophages, could potentially display osteoclast-like functions. Objective: To characterize the phenotype of macrophages located in areas surrounding the calcium deposits in human atherosclerotic plaques...
April 24, 2017: Circulation Research
https://www.readbyqxmd.com/read/28428204/flow-perturbation-mediates-neutrophil-recruitment-and-potentiates-endothelial-injury-via-tlr2-in-mice-implications-for-superficial-erosion
#12
Grégory Franck, Thomas Mawson, Grasiele Sausen, Manuel Salinas, Gustavo Santos Masson, Andrew P Cole, Marina Beltrami Moreira, Yiannis Chatzizisis, Thibaut Quillard, Yevgenia Tesmenitsky, Eugenia Shvartz, Galina K Sukhova, Filip K Swirski, Matthias Nahrendorf, Elena Aikawa, Kevin Croce, Peter Libby
Rationale: Superficial erosion currently causes up to a third of acute coronary syndromes (ACS), yet we lack understanding of its mechanisms. Thrombi due to superficial intimal erosion characteristically complicate matrix-rich atheromata in regions of flow perturbation. Objective: This study tested in vivo the involvement of disturbed flow, and of neutrophils, hyaluronan, and TLR2 ligation in superficial intimal injury, a process implicated in superficial erosion. Methods and Results: In mouse carotid arteries with established intimal lesions tailored to resemble the substrate of human eroded plaques, acute flow perturbation promoted downstream endothelial cell (EC) activation, neutrophil accumulation, EC death and desquamation, and mural thrombosis...
April 20, 2017: Circulation Research
https://www.readbyqxmd.com/read/28420669/a-possible-early-biomarker-for-bicuspid-aortopathy-circulating-transforming-growth-factor-beta-1-to-soluble-endoglin-ratio
#13
Amalia Forte, Ciro Bancone, Gilda Cobellis, Marianna Buonocore, Giuseppe Santarpino, Theodor Fischlein, Marilena Cipollaro, Marisa De Feo, Alessandro Della Corte
Rationale: The pathogenesis of bicuspid aortic valve (BAV)-associated aortopathy is poorly understood and no prognostic biomarker is currently available. Objective: We aimed to identify putative circulating biomarkers pathogenetically and prognostically linked to bicuspid aortopathy. Methods and Results: By RT-PCR, we evaluated gene expression variations (versus normal aorta) of transforming growth factor-beta1 (TGF-β1), connective tissue growth factor (CTGF), matrix metalloproteinase-2 (MMP-2), MMP-14, endoglin (ENG) and superoxide dismutase 3 (SOD3) in ascending aorta samples from 50 tricuspid and 70 BAV patients undergoing surgery for aortic stenosis (aorta diameter ≤45mm: BAVnon-dil or >45mm: BAVdil)...
April 18, 2017: Circulation Research
https://www.readbyqxmd.com/read/28420668/hypercholesterolemia-induces-differentiation-of-regulatory-t-cells-in-the-liver
#14
Reiner K Mailer, Anton Gisterå, Konstantinos A Polyzos, Daniel F Ketelhuth, Göran K Hansson
Rationale: The liver is the central organ that responds to dietary cholesterol intake and facilitates the release and clearance of lipoprotein particles. Persistent hypercholesterolemia leads to immune responses against lipoprotein particles that drive atherosclerosis. However, the effect of hypercholesterolemia on hepatic T cell differentiation remains unknown. Objective: To investigate hepatic T cell subsets upon hypercholesterolemia. Methods and Results: We observed that hypercholesterolemia elevated the intrahepatic regulatory T (Treg) cell population and increased the expression of transforming growth factor beta 1 in the liver...
April 18, 2017: Circulation Research
https://www.readbyqxmd.com/read/28404615/myeloperoxidase-mediates-postischemic-arrhythmogenic-ventricular-remodeling
#15
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/28400398/multi-imaging-method-to-assay-the-contractile-mechanical-output-of-micropatterned-human-ipsc-derived-cardiac-myocytes
#16
Alexandre J Ribeiro, Olivier Schwab, Mohammad A Mandegar, Yen-Sin Ang, Bruce R Conklin, Deepak Srivastava, Beth L Pruitt
Rationale: During each beat, cardiac myocytes generate the mechanical output necessary for heart function through contractile mechanisms that involve shortening of sarcomeres along myofibrils. Human induced pluripotent stem cells can be differentiated into cardiac myocytes that model cardiac contractile mechanical output more robustly when micropatterned into physiological shapes. Quantifying the mechanical output of these cells enables us to assay cardiac activity in a dish. Objective: We sought to develop a computational platform that integrates analytical approaches to quantify the mechanical output of single micropatterned cardiac myocytes from microscopy videos...
April 11, 2017: Circulation Research
https://www.readbyqxmd.com/read/28381400/association-of-plasma-7-ketocholesterol-with-cardiovascular-outcomes-and-total-mortality-in-patients-with-coronary-artery-disease
#17
Jiayi Song, Duan Wang, Hongen Chen, Xiuwei Huang, Yuan Zhong, Nan Jiang, Chaogang Chen, Min Xia
Rationale: 7-Ketocholesterol (7-KC), a form of cholesterol oxidation product, plays an essential role in the atherogenesis in animal models. Objective: We sought to determine the association of circulating 7-KC with clinical cardiovascular outcomes and total mortality in patients with stable coronary artery disease (CAD). Methods and Results: We measured the plasma 7-KC levels by high performance liquid chromatography in a prospective cohort study of 1016 patients (mean age 63.2 years, male 61.1%) with stable CAD who were recruited from December 2008 to December 2011, and followed up for a median of 4...
April 5, 2017: Circulation Research
https://www.readbyqxmd.com/read/28373350/social-integration-and-reduced-risk-of-coronary-heart-disease-in-women-the-role-of-lifestyle-behaviors
#18
Shun-Chiao Chang, Maria Glymour, Marilyn Cornelis, Stefan Walter, Eric Rimm, Eric T Tchetgen, Ichiro Kawachi, Laura D Kubzansky
Rationale: Higher social integration is associated with lower cardiovascular mortality; however, whether it is associated with incident coronary heart disease (CHD), especially in women, and if associations differ by case fatality is unclear. Objective: This study sought to examine the associations between social integration and risk of incident CHD in a large female prospective cohort. Methods and Results: 76,362 women in the Nurses' Health Study (NHS), free of CHD and stroke at baseline (1992), were followed until 2014...
April 3, 2017: Circulation Research
https://www.readbyqxmd.com/read/28373349/methodological-rigor-in-preclinical-cardiovascular-studies-targets-to-enhance-reproducibility-and-promote-research-translation
#19
F Daniel Ramirez, Pouya Motazedian, Richard G Jung, Pietro Di Santo, Zachary D MacDonald, Robert Moreland, Trevor Simard, Aisling A Clancy, Juan Russo, Vivian A Welch, George A Wells, Benjamin Hibbert
Rationale: Methodological sources of bias and suboptimal reporting contribute to irreproducibility in preclinical science and may negatively impact research translation. Randomization, blinding, sample size estimation, and considering sex as a biological variable are deemed crucial study design elements to maximize the quality and predictive value of preclinical experiments. Objective: To examine the prevalence and temporal patterns of recommended study design element implementation in preclinical cardiovascular research...
April 3, 2017: Circulation Research
https://www.readbyqxmd.com/read/28356340/analysis-of-cardiac-myocyte-maturation-using-casaav-a-platform-for-rapid-dissection-of-cardiac-myocyte-gene-function-in-vivo
#20
Yuxuan Guo, Nathan J VanDusen, Lina Zhang, Weiliang Gu, Isha Sethi, Silvia Guatimosim, Qing Ma, Blake D Jardin, Yulan Ai, Donghui Zhang, Biyi Chen, Ang Guo, Guo-Cheng Yuan, Long-Sheng Song, William T Pu
Rationale: Loss-of-function studies in cardiac myocytes (CMs) are currently limited by the need for appropriate conditional knockout alleles. The factors that regulate CM maturation are poorly understood. Prior studies on CM maturation have been confounded by heart dysfunction caused by whole organ gene inactivation. Objective: To develop a new technical platform to rapidly characterize cell-autonomous gene function in postnatal murine CMs and apply it to identify genes that regulate T-tubules, a hallmark of mature cardiac myocytes...
March 29, 2017: Circulation Research
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