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Circulation Research

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https://www.readbyqxmd.com/read/28428204/flow-perturbation-mediates-neutrophil-recruitment-and-potentiates-endothelial-injury-via-tlr2-in-mice-implications-for-superficial-erosion
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/28356339/nicotinamide-phosphoribosyltransferase-in-smooth-muscle-cells-maintains-genome-integrity-resists-aortic-medial-degeneration-and-is-suppressed-in-human-thoracic-aortic-aneurysm-disease
#10
Alanna Watson, Zengxuan Nong, Hao Yin, Caroline O'Neil, Stephanie Fox, Brittany Balint, Ray Guo, Oberdan Leo, Michael W Chu, Robert Gros, J G Pickering
Rationale: The thoracic aortic wall can degenerate over time with catastrophic consequences. Vascular smooth muscle cells (SMCs) can resist and repair artery damage but their capacities decline with age and stress. Recently, cellular production of NAD(+) via nicotinamide phosphoribosyltransferase (Nampt) has emerged as a mediator of cell vitality. However, a role for Nampt in aortic SMCs in vivo is unknown. Objective: To determine if a Nampt-NAD(+) control system exists within the aortic media and is required for aortic health...
March 29, 2017: Circulation Research
https://www.readbyqxmd.com/read/28351842/minute-myocardial-injury-as-measured-by-high-sensitive-troponin-t-serum-levels-predicts-the-response-to-intracoronary-infusion-of-bone-marrow-derived-mononuclear-cells-in-patients-with-stable-chronic-post-infarction-heart-failure-insights-from-the-topcare-chd
#11
Brigitte Luu, David M Leistner, Eva Herrmann, Florian H Seeger, Joerg Honold, Stephan Fichtlscherer, Andreas M Zeiher, Birgit Assmus
Rationale: Cell-based therapies are a promising option in patients with chronic post-infarction heart failure (ICM). However, the responses following intracoronary infusion of autologous bone marrow-derived mononuclear cells (BMC) are heterogeneous, which may be related to impaired cell retention in patients with ICM. Ischemic injury is associated with upregulation of prototypical chemoattractant cytokines mediating retention and homing of circulating cells. The development of ultrasensitive tests to measure troponin-T serum levels (hs-TnT) revealed the presence of ongoing minute myocardial injury even in patients with stable ICM...
March 28, 2017: Circulation Research
https://www.readbyqxmd.com/read/28348007/genome-wide-analysis-of-dna-methylation-and-acute-coronary-syndrome
#12
Jun Li, Xiaoyan Zhu, Kuai Yu, Haijing Jiang, Yizhi Zhang, Siyun Deng, Longxian Cheng, Xuezhen Liu, Jia Zhong, Xiaomin Zhang, Mei'an He, Weihong Chen, Jing Yuan, Ming Gao, Yansen Bai, Xu Han, Bing Liu, Xiaoting Luo, Wenhua Mei, Xiaosheng He, Shunchang Sun, Liyun Zhang, Hesong Zeng, Huizhen Sun, Chuanyao Liu, Yanjun Guo, Bing Zhang, Zhihong Zhang, Jinyan Huang, An Pan, Yu Yuan, Francesca Angileri, Bingxia Ming, Fang Zheng, Qiutang Zeng, Xiaobo Mao, Yudong Peng, Yi Mao, Ping Ye, Qing K Wang, Lu Qi, Frank B Hu, Liming Liang, Tangchun Wu
Rationale: Acute coronary syndrome (ACS) is a leading cause of death worldwide. Immune functions play a vital role in ACS development, however, whether epigenetic modulation contributes to the regulation of blood immune cells in this disease has not been investigated. Objective: We conducted an epigenome-wide analysis with circulating immune cells to identify differentially methylated genes in ACS. Methods and Results: We examined genome-wide methylation of whole blood in 102 ACS patients and 101 controls using HumanMethylation450 array, and externally replicated significant discoveries in 100 patients and 102 controls...
March 27, 2017: Circulation Research
https://www.readbyqxmd.com/read/28325782/aibp-limits-angiogenesis-through-%C3%AE-secretase-mediated-upregulation-of-notch-signaling
#13
Renfang Mao, Shu Meng, Qilin Gu, Raquel Araujo-Gutierrez, Sandeep Kumar, Qing Yan, Felicidad Almazan, Keith A Youker, Yingbin Fu, Henry J Pownall, John P Cooke, Yury I Miller, Longhou Fang
Rationale: Angiogenesis improves perfusion to the ischemic tissue following acute vascular obstruction. Angiogenesis in pathophysiological settings reactivates signaling pathways involved in developmental angiogenesis. We showed previously that apoA-I binding protein (AIBP)-regulated cholesterol efflux in endothelial cells (ECs) controls zebrafish embryonic angiogenesis. Objective: This study is to determine whether loss of AIBP affects angiogenesis in mice during development and under pathological conditions, and to explore the underlying molecular mechanism...
March 21, 2017: Circulation Research
https://www.readbyqxmd.com/read/28325781/20-hete-signals-through-g-protein-coupled-receptor-gpr75-gq-to-affect-vascular-function-and-trigger-hypertension
#14
Victor Garcia, Ankit Gilani, Brian Shkolnik, Varunkumar Pandey, Frank F Zhang, Rambabu Dakarapu, Shyam K Gandham, N R Reddy, Joan P Graves, Artiom Gruzdev, Darryl C Zeldin, Jorge H Capdevila, John R Falck, Michal L Schwartzman
Rationale: 20-Hydroxyeicosatetraenoic acid (20-HETE), one of the principle cytochrome P450 (CYP) eicosanoids, is a potent vasoactive lipid whose vascular effects include stimulation of smooth muscle contractility, migration and proliferation, as well as endothelial cell dysfunction and inflammation. Increased levels of 20-HETE in experimental animals and in humans are associated with hypertension, stroke, myocardial infarction and vascular diseases. Objective: To date, a receptor/binding site for 20-HETE has been implicated based on the use of specific agonists and antagonists...
March 21, 2017: Circulation Research
https://www.readbyqxmd.com/read/28302649/endothelial-protective-monocyte-patrolling-in-large-arteries-intensified-by-western-diet-and-atherosclerosis
#15
Amado Quintar, Sara McArdle, Dennis Wolf, Alex Marki, Erik Ehinger, Melanie Vassallo, Jacqueline F Miller, Zbigniew Mikulski, Klaus Ley, Konrad Buscher
Rationale: Non-classical mouse monocyte (CX3CR1(high), Ly-6C(low)) patrolling along the vessels of the microcirculation is critical for endothelial homeostasis and inflammation. Due to technical challenges it is currently not established how patrolling occurs in large arteries. Objective: This study was undertaken to elucidate the molecular, migratory and functional phenotype of patrolling monocytes in the high shear and pulsatile environment of large arteries in healthy, hyperlipidemic and atherosclerotic conditions...
March 16, 2017: Circulation Research
https://www.readbyqxmd.com/read/28298297/angiogenic-mechanisms-of-human-cd34-stem-cell-exosomes-in-the-repair-of-ischemic-hindlimb
#16
Prabhu Mathiyalagan, Yaxuan Liang, David Kim, Sol Misener, Tina Thorne, Christine Kamide, Ekaterina Klyachko, Douglas W Losordo, Roger J Hajjar, Susmita Sahoo
Rationale: Paracrine secretions appear to mediate therapeutic effects of human CD34(+) stem cells locally transplanted in patients with myocardial and critical limb ischemia as well as in animal models. Earlier, we had discovered that paracrine secretion from human CD34(+) cells contains pro-angiogenic, membrane-bound nano-vesicles called exosomes (CD34Exo). Objective: Here, we investigated the mechanisms of CD34Exo-mediated ischemic tissue repair and therapeutic angiogenesis by studying their miRNA content and uptake...
March 15, 2017: Circulation Research
https://www.readbyqxmd.com/read/28298296/fabrication-of-synthetic-mesenchymal-stem-cells-for-the-treatment-of-acute-myocardial-infarction-in-mice
#17
Lan Luo, Junnan Tang, Kodai Nishi, Chen Yan, Phuong-Uyen Dinh, Jhon Cores, Takashi Kudo, Jinying Zhang, Tao-Sheng Li, Ke Cheng
Rationale: Stem cell therapy faces a number of challenges. It is difficult to grow, preserve, and transport stem cells before they are administered to the patient. Synthetic analogs for stem cells represent a new approach to overcome these hurdles and hold the potential to revolutionize regenerative medicine. Objective: We aim to fabricate synthetic analogs of stem cells and test their therapeutic potential for treatment of acute myocardial infarction in mice. Methods and Results: We packaged secreted factors from human bone marrow-derived mesenchymal stem cells (MSC) into Poly(lactic-co-glycolic acid) PLGA microparticles and then coated them with MSC membranes...
March 15, 2017: Circulation Research
https://www.readbyqxmd.com/read/28298295/t-cell-mineralocorticoid-receptor-controls-blood-pressure-by-regulating-interferon-gamma
#18
Xue Nan Sun, Chao Li, Yuan Liu, Lin-Juan Du, Meng-Ru Zeng, Xiao Jun Zheng, Wu Chang Zhang, Yan Liu, Mingjiang Zhu, Deping Kong, Li Zhou, Limin Lu, Zhu-Xia Shen, Yi Yi, Lili Du, Mu Qin, Xu Liu, Zichun Hua, Shuyang Sun, Huiyong Yin, Bin Zhou, Ying Yu, Zhiyuan Zhang, Sheng-Zhong Duan
Rationale: Hypertension remains to be a global public health burden and demands novel intervention strategies such as targeting T cells and T cell-derived cytokines. Mineralocorticoid receptor (MR) antagonists have been clinically used to treat hypertension. However, the function of T cell MR in blood pressure (BP) regulation has not been elucidated. Objective: We aim to determine the role of T cell MR in BP regulation and to explore the mechanism. Methods and Results: Using T cell MR knockout (TMRKO) mouse in combination with angiotensin II (AngII)-induced hypertensive mouse model, we demonstrated that MR deficiency in T cells strikingly decreased both systolic and diastolic BP, and attenuated renal and vascular damage...
March 15, 2017: Circulation Research
https://www.readbyqxmd.com/read/28298294/vegfr3-modulates-vascular-permeability-by-controlling-vegf-vegfr2-signaling
#19
Krista Heinolainen, Sinem Karaman, Gabriela D'Amico, Tuomas Tammela, Raija Sormunen, Lauri Eklund, Kari Alitalo, Georgia Zarkada
Rationale: Vascular endothelial growth factor (VEGF) is the main driver of angiogenesis and vascular permeability via VEGF receptor 2 (VEGFR2), while lymphangiogenesis signals are transduced by VEGFC/D via VEGFR3. VEGFR3 also regulates sprouting angiogenesis and blood vessel growth, but to what extent VEGFR3 signaling controls blood vessel permeability remains unknown. Objective: To investigate the role of VEGFR3 in the regulation of VEGF-induced vascular permeability. Methods and Results: Long-term global Vegfr3 gene deletion in adult mice resulted in increased fibrinogen deposition in lungs and kidneys, indicating enhanced vascular leakage at the steady state...
March 15, 2017: Circulation Research
https://www.readbyqxmd.com/read/28289018/adrenergic-signaling-strengthens-cardiac-myocyte-cohesion
#20
Camilla Schinner, Franziska Vielmuth, Vera Rötzer, Matthias Hiermaier, Mariya Radeva, Thu K Co, Eva Hartlieb, Andreas Schmidt, Axel Imhof, Ahmed Messoudi, Anja Horn, Angela Schlipp, Volker Spindler, Jens Waschke
Rationale: The sympathetic nervous system is a major mediator of heart function. Intercalated discs (ICDs) composed of desmosomes, adherens junctions and gap junctions provide the structural backbone for coordinated contraction of cardiac myocytes. Objective: Gap junctions dynamically remodel to adapt to sympathetic signaling. However, it is unknown whether such rapid adaption also occurs for the adhesive function provided by desmosomes and adherens junctions. Methods and Results: Atomic force microscopy revealed that β-adrenergic signaling enhances both the number of desmoglein 2 (Dsg2) -specific interactions along cell junctions and the mean Dsg2-mediated binding forces, whereas N-cadherin-mediated interactions were not affected...
March 13, 2017: Circulation Research
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