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Circulation Research

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https://www.readbyqxmd.com/read/27908912/a-deep-proteome-analysis-identifies-the-complete-secretome-as-the-functional-unit-of-human-cardiac-progenitor-cells
#1
Sudhish Sharma, Rachana Mishra, Grace E Bigham, Brody Wehman, Mohd M Khan, Huichun Xu, Progyaparamita Saha, Young Ah Goo, Srinivisa R Datla, Ling Chen, Mohan E Tulapurkar, Bradley S Taylor, Peixin Yang, Sotirios K Karathanasis, David R Goodlett, Sunjay Kaushal
RATIONALE: Cardiac progenitor cells are an attractive cell type for tissue regeneration but their mechanism for myocardial remodeling is still unclear. OBJECTIVE: This investigation determines how chronological age influences the phenotypic characteristics and the secretome of human cardiac progenitor cells (CPCs), as well as their potential to recover injured myocardium. METHODS AND RESULTS: Adult (aCPCs) and neonatal (nCPCs) cells were derived from patients more than 40 years or less than one month of age, respectively, and their functional potential was determined in a rodent myocardial infarction (MI) model...
December 1, 2016: Circulation Research
https://www.readbyqxmd.com/read/27903568/effects-of-trans-endocardial-delivery-of-bone-marrow-derived-cd133-cells-on-left-ventricle-perfusion-and-function-in-patients-with-refractory-angina-final-results-of-randomized-double-blinded-placebo-controlled-regent-vsel-trial
#2
Wojciech Wojakowski, Tomasz Jadczyk, Aleksandra Michalewska-Wludarczyk, Zofia Parma, Miroslaw Markiewicz, Wojciech Rychlik, Magdalena Kostkiewicz, Katarzyna Gruszczynska, Anna Blach, Monika Dzierzak-Mietla, Wojciech Wanha, Joanna Ciosek, Beata Ochala, Lukasz Rzeszutko, Wieslaw Cybulski, Lukasz Partyka, Wojciech Zasada, Witold Wludarczyk, Sebastian Dworowy, Waclaw B Kuczmik, Grzegorz Smolka, Tomasz Z Pawlowski, Andrzej Ochala, Michal Tendera
RATIONALE: New therapies for refractory angina are needed. OBJECTIVE: Assessment of trans-endocardial delivery of bone marrow (BM) CD133(+)cells in patients with refractory angina. METHODS AND RESULTS: Randomized, double-blinded, placebo-controlled trial enrolled 31 patients with recurrent CCS II-IV angina despite optimal medical therapy, ≥ one myocardial segment with inducible ischemia in Tc-99m SPECT who underwent BM biopsy and were allocated to cells (n=16) or placebo (n=15)...
November 30, 2016: Circulation Research
https://www.readbyqxmd.com/read/27903567/increased-plasma-ige-accelerate-atherosclerosis-in-secreted-igm-deficiency
#3
Dimitrios Tsiantoulas, Ilze Bot, Maria Ozsvar Kozma, Laura Goederle, Thomas Perkmann, Karsten Hartvigsen, Daniel H Conrad, Johan Kuiper, Ziad Mallat, Christoph J Binder
RATIONALE: Deficiency of secreted IgM (sIgM(-/-)) accelerates atherosclerosis in Ldlr(-/-) mice. Several atheroprotective effects of increased levels of IgM antibodies have been suggested, including preventing inflammation induced by oxidized LDL and promoting apoptotic cell clearance. However, the mechanisms by which the lack of sIgM promotes lesion formation remain unknown. OBJECTIVE: To identify the mechanisms by which sIgM deficiency accelerates atherosclerosis in mice...
November 30, 2016: Circulation Research
https://www.readbyqxmd.com/read/27899403/meta-analysis-of-genome-wide-association-studies-for-abdominal-aortic-aneurysm-identifies-four-new-disease-specific-risk-loci
#4
Gregory T Jones, Gerard Tromp, Helena Kuivaniemi, Solveig Gretarsdottir, Annette F Baas, Betti Giusti, Ewa Strauss, Femke N van 't Hof, Thomas Webb, Robert Erdman, Marylyn D Ritchie, James R Elmore, Anurag Verma, Sarah Pendergrass, Iftikhar J Kullo, Zi Ye, Peggy L Peissig, Omri Gottesman, Shefali S Verma, Jennifer Malinowski, Laura J Rasmussen-Torvik, Kenneth Borthwick, Diane T Smelser, David R Crosslin, Mariza de Andrade, Evan J Ryer, Catherine A McCarty, Erwin P Bottinger, Jennifer A Pacheco, Dana C Crawford, David S Carrell, Glenn S Gerhard, David P Franklin, David J Carey, Victoria L Phillips, Michael J Williams, Wenhua Wei, Ross Blair, Andrew A Hill, Thodur M Vasudevan, David R Lewis, Ian A Thomson, Jo Krysa, Geraldine B Hill, Justin Roake, Tony R Merriman, Grzegorz Oszkinis, Silvia Galora, Claudia Saracini, Rosanna Abbate, Raffaele Pulli, Carlo Pratesi, Athanasios Saratzis, Anna Verissimo, Suzannah J Bumpstead, Stephen A Badger, Rachel E Clough, Gillian W Cockerill, Hany Hafez, D J Scott, T S Futers, Simon P Romaine, Katherine Bridge, Kathryn J Griffin, Marc A Bailey, Alberto Smith, Matt M Thompson, Frank van Bockxmeer, Stefan E Matthiasson, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Jan D Blankensteijn, Joep A Teijink, Cisca Wijmenga, Jacqueline de Graaf, Lambertus A Kiemeney, Jes S Lindholt, Anne E Hughes, Declan T Bradley, Kathleen Stirrups, Jonathan Golledge, Paul E Norman, Janet T Powell, Steve E Humphries, Stephen E Hamby, Alison H Goodall, Christopher P Nelson, Natzi Sakalihasan, Audrey Courtois, Robert E Ferrell, Per Eriksson, Lasse Folkersen, Anders Franco-Cereceda, John D Eicher, Andrew D Johnson, Christer Betsholtz, Arno Ruusalepp, Oscar Franzén, Eric Schadt, Johan L Björkegren, Leonard Lipovich, Anne M Drolet, Eric Verhoeven, Clark J Zeebregts, Robert H Geelkerken, Marc R van Sambeek, Steven M van Sterkenburg, Jean-Paul P de Vries, Kari Stefansson, John R Thompson, Paul I de Bakker, Panos Deloukas, Robert D Sayers, Seamus Harrison, Andre M van Rij, Nilesh J Samani, Matthew J Bown
RATIONALE: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. OBJECTIVE: To identify additional AAA risk loci using data from all available genome-wide association studies (GWAS). METHODS AND RESULTS: Through a meta-analysis of 6 GWAS datasets and a validation study totalling 10,204 cases and 107,766 controls we identified 4 new AAA risk loci: 1q32...
November 29, 2016: Circulation Research
https://www.readbyqxmd.com/read/27895035/microrna-210-enhances-fibrous-cap-stability-in-advanced-atherosclerotic-lesions
#5
Suzanne M Eken, Hong Jin, Ekaterina Chernogubova, Yuhuang Li, Nancy Simon, Changyan Sun, Greg Korzunowicz, Albert Busch, Alexandra Bäcklund, Cecilia Österholm, Anton Razuvaev, Thomas Renné, Hans-Henning Eckstein, Jaroslav Pelisek, Per Eriksson, Maria Gonzalez Diez, Ljubica P Matic Perisic, Isabel N Schellinger, Uwe Raaz, Nicholas J Leeper, Göran K Hansson, Gabrielle Paulsson-Berne, Ulf Hedin, Lars Maegdefessel
RATIONALE: In the search for markers and modulators of vascular disease, miRNAs have emerged as potent therapeutic targets. OBJECTIVE: To investigate miRNAs of clinical interest in patients with unstable carotid stenosis at risk of stroke. METHODS AND RESULTS: Utilizing patient material from the Biobank of Karolinska Endarterectomies (BiKE), we profiled miRNA expression in patients with stable vs unstable carotid plaque. A PCR-based miRNA array of plasma, sampled at the carotid lesion site, identified eight deregulated miRNAs (miR-15b, -29c, -30c/d, -150, -191, -210 and -500)...
November 28, 2016: Circulation Research
https://www.readbyqxmd.com/read/27879282/sex-related-discordance-between-aortic-valve-calcification-and-hemodynamic-severity-of-aortic-stenosis-is-valvular-fibrosis-the-explanation
#6
Louis Simard, Nancy Côté, François Dagenais, Patrick Mathieu, Christian Couture, Sylvain Trahan, Yohan Bossé, Siamak Mohammadi, Sylvain Pagé, Philippe Joubert, Marie-Annick Clavel
RATIONALE: Calcific aortic stenosis (AS) is characterized by calcium deposition in valve leaflets. However, women present lower aortic valve calcification (AVC) loads than men for the same AS hemodynamic severity. OBJECTIVE: We thus aimed to assess sex-differences in aortic valve fibro-calcific remodelling. METHODS AND RESULTS: One hundred and twenty-five patients underwent Doppler-echocardiography and multidetector-computed-tomography within 3 months prior to aortic valve replacement...
November 22, 2016: Circulation Research
https://www.readbyqxmd.com/read/27872050/experimental-systems-and-computational-approaches-to-understanding-the-microrna-mediated-reparative-potential-of-cardiac-progenitor-cell-derived-exosomes-from-pediatric-patients
#7
Udit Agarwal, Alex George, Srishti Bhutani, Shohini Ghosh-Choudhary, Josh T Maxwell, Milton E Brown, Yash Mehta, Manu O Platt, Yaxuan Liang, Susmita Sahoo, Michael E Davis
RATIONALE: Studies have demonstrated that exosomes can repair cardiac tissue post myocardial infarction (MI) and recapitulate the benefits of cellular therapy. OBJECTIVE: We evaluated the role of donor age and hypoxia of human pediatric cardiac progenitor cell (CPC)-derived exosomes, in a rat model of ischemia reperfusion (IR) injury. METHODS AND RESULTS: Human CPCs from the right atrial appendages from children of different ages undergoing cardiac surgery for congenital heart defects were isolated and cultured under hypoxic or normoxic conditions...
November 21, 2016: Circulation Research
https://www.readbyqxmd.com/read/27872049/contribution-of-kv1-5-channel-to-h2o2-induced-human-arteriolar-dilation-and-its-modulation-by-coronary-artery-disease
#8
Yoshinori Nishijima, Sheng Cao, Dawid S Chabowski, Ankush Korishettar, Alyce Ge, Xiaodong Zheng, Rodney Sparapani, David D Gutterman, David X Zhang
RATIONALE: Hydrogen peroxide (H2O2) regulates vascular tone in the human microcirculation under physiological and pathophysiological conditions. It dilates arterioles by activating BKCa channels in subjects with coronary artery disease (CAD), but its mechanisms of action in subjects without CAD (non-CAD) as compared to those with CAD remain unknown. OBJECTIVE: We hypothesize that H2O2-elicited dilation involves different K(+) channels in non-CAD versus CAD, resulting in an altered capacity for vasodilation during disease...
November 21, 2016: Circulation Research
https://www.readbyqxmd.com/read/27856497/intravenous-allogeneic-mesenchymal-stem-cells-for-non-ischemic-cardiomyopathy-safety-and-efficacy-results-of-a-phase-ii-a-randomized-trial
#9
Javed Butler, Stephen E Epstein, Stephen J Greene, Arshed A Quyyumi, Sergey Sikora, Raymond J Kim, Allen S Anderson, Jane E Wilcox, Nikolai I Tankovich, Michael J Lipinski, Yi-An Ko, Kenneth B Margulies, Robert T Cole, Hal A Skopicki, Mihai Gheorghiade
RATIONALE: Potential benefits of mesenchymal stem cell (MSC) therapy in heart failure (HF) may be related to paracrine properties and systemic effects, including anti-inflammatory activities. If this hypothesis is valid, intravenous administration of MSCs should improve outcomes in HF, an entity in which excessive chronic inflammation may play a pivotal role. OBJECTIVE: To assess the safety and preliminary efficacy of intravenously administered ischemia tolerant MSCs (itMSCs) in patients with non-ischemic cardiomyopathy...
November 16, 2016: Circulation Research
https://www.readbyqxmd.com/read/27834190/differentiated-smooth-muscle-cells-generate-a-subpopulation-of-resident-vascular-progenitor-cells-in-the-adventitia-regulated-by-klf4
#10
Mark W Majesky, Henrick Horita, Allison Ostriker, Sizhao Lu, Jenna N Regan, Ashim K Bagchi, Xiu R Dong, Joanna M Poczobutt, Raphael A Nemenoff, Mary C Weiser-Evans
RATIONALE: The vascular adventitia is a complex layer of the vessel wall consisting of vasa vasorum microvessels, nerves, fibroblasts, immune cells, and resident progenitor cells. Adventitial progenitors express the stem cell markers, Sca1 and CD34 (AdvSca1 cells), have the potential to differentiate in vitro into multiple lineages, and potentially contribute to intimal lesions in vivo. OBJECTIVE: While emerging data support the existence of AdvSca1 cells, the goal of this study was to determine their origin, degree of multipotency and/or heterogeneity, and contribution to vessel remodeling...
November 9, 2016: Circulation Research
https://www.readbyqxmd.com/read/27821724/preserve-ami-a-randomized-double-blind-placebo-controlled-clinical-trial-of-intracoronary-administration-of-autologous-cd34-cells-in-patients-with-left-ventricular-dysfunction-post-stemi
#11
Arshed A Quyyumi, Alejandro Vasquez, Dean Kereiakes, Marc Klapholz, Gary L Schaer, Ahmed Abdel-Latif, Stephen Frohwein, Timothy D Henry, Richard A Schatz, Nabil Dib, Catalin Toma, Charles J Davidson, Gregory W Barsness, David Shavelle, Martin Cohen, Joseph Poole, Thomas J Moss, Pamela Hyde, AnnaMaria Kanakaraj, Vitaly Druker, Amy Chung, Candice Junge, Robert A Preti, Robin L Smith, David J Mazzo, Andrew Pecora, Douglas W Losordo
RATIONALE: Despite direct immediate intervention and therapy, ST segment Elevation Myocardial Infarction (STEMI) victims remain at risk for infarct expansion, heart failure, re-infarction, repeat revascularization and death. OBJECTIVE: To evaluate the safety and bioactivity of autologous CD34+ cell (CLBS10) intracoronary infusion in patients with left ventricular dysfunction (LVD) post-STEMI. METHODS AND RESULTS: Patients who underwent successful stenting for STEMI and had LVD (ejection fraction [EF] ≤48%) ≥4 days post-stent were eligible for enrollment...
November 7, 2016: Circulation Research
https://www.readbyqxmd.com/read/27821723/c1q-tnf-related-protein-9-promotes-cardiac-hypertrophy-and-failure
#12
Mahesh Appari, Astrid Breitbart, Florian Brandes, Malgorzata Szaroszyk, Natali Froese, Mortimer Korf-Klingebiel, Mona Malek Mohammadi, Andrea Grund, Gesine M Scharf, Honghui Wang, Carolin Zwadlo, Daniela Fraccarollo, Ulrike Schrameck, Mona Nemer, William Wong, Hugo A Katus, Kai C Wollert, Oliver J Müller, Johann Bauersachs, Joerg Heineke
RATIONALE: Myocardial endothelial cells promote cardiomyocyte hypertrophy, possibly through the release of growth factors. The identity of these factors, however, remains largely unknown, and we hypothesized here that the secreted C1q-TNF-related protein-9 (CTRP9) might act as endothelial derived protein to modulate heart remodeling in response to pressure overload. OBJECTIVE: To examine the source of cardiac CTRP9 and its function during pressure overload. METHODS AND RESULTS: CTRP9 was mainly derived from myocardial capillary endothelial cells...
November 7, 2016: Circulation Research
https://www.readbyqxmd.com/read/27799254/phosphodiesterase-2-protects-against-catecholamine-induced-arrhythmia-and-preserves-contractile-function-after-myocardial-infarction
#13
Christiane Vettel, Marta Lindner, Matthias Dewenter, Kristina Lorenz, Constanze Schanbacher, Merle Riedel, Simon Lämmle, Simone Meinecke, Fleur E Mason, Samuel Sossalla, Andreas Geerts, Michael Hoffmann, Frank Wunder, Fabian J Brunner, Thomas Wieland, Hind Mehel, Sarah Karam, Patrick Lechêne, Jérôme Leroy, Grégoire Vandecasteele, Michael Wagner, Rodolphe Fischmeister, Ali El-Armouche
RATIONALE: Phosphodiesterase 2 (PDE2) is a dual substrate esterase, which has the unique property to be stimulated by cGMP, but primarily hydrolyses cAMP. Myocardial PDE2 is upregulated in human heart failure (HF), but its role in the heart is unknown. OBJECTIVE: To explore the role of PDE2 in cardiac function, propensity to arrhythmia and in myocardial infarction. METHODS AND RESULTS: Pharmacological inhibition of PDE2 (BAY 60-7550, BAY) led to a significant positive chronotropic effect on top of maximal β-adrenoceptor (β-AR) activation in healthy mice...
October 31, 2016: Circulation Research
https://www.readbyqxmd.com/read/27799253/hypertension-linked-pathophysiological-alterations-in-the-gut
#14
Monica M Santisteban, Yanfei Qi, Jasenka Zubcevic, Seungbum Kim, Tao Yang, Vinayak Shenoy, Colleen T Cole-Jeffrey, Gilberto O Lobaton, Daniel C Stewart, Andres Rubiano, Chelsey S Simmons, Fernando Garcia-Pereira, Richard D Johnson, Carl J Pepine, Mohan K Raizada
RATIONALE: Sympathetic nervous system control of inflammation plays a central role in hypertension. The gut receives significant sympathetic innervation, is densely populated with a diverse microbial ecosystem, and contains immune cells that greatly impact overall inflammatory homeostasis. Despite this uniqueness, little is known about the involvement of the gut in hypertension. OBJECTIVE: Test the hypothesis that increased sympathetic drive to the gut is associated with increased gut wall permeability, increased inflammatory status, and microbial dysbiosis and that these gut pathological changes are linked to hypertension...
October 31, 2016: Circulation Research
https://www.readbyqxmd.com/read/27799252/diagnostic-and-prognostic-utility-of-circulating-cytochrome-c-in-acute-myocardial-infarction
#15
Giancarlo Marenzi, Nicola Cosentino, Jasper Boeddinghaus, Mirella Trinei, Marco Giorgio, Valentina Milazzo, Marco Moltrasio, Daniela Cardinale, Maria Teresa Sandri, Fabrizio Veglia, Alice Bonomi, Max Kaech, Raphael Twerenbold, Thomas Nestelberger, Tobias Reichlin, Karin Wildi, Samyut Shrestha, Nikola Kozhuharov, Zaid Sabti, Carlo M Cipolla, Christian Mueller, Antonio L Bartorelli
RATIONALE: In contrast to cardiomyocyte necrosis, which can be quantified by cardiac troponin (cTn), functional cardiomyocyte impairment, including mitochondrial dysfunction, has escaped clinical recognition in acute myocardial infarction (AMI) patients. OBJECTIVE: To investigate the diagnostic accuracy for AMI and prognostic prediction of in-hospital mortality of cytochrome c Methods and Results: We prospectively assessed cytochrome c serum levels at hospital presentation in two cohorts: a diagnostic cohort of patients presenting with suspected AMI, and a prognostic cohort of definite AMI patients...
October 31, 2016: Circulation Research
https://www.readbyqxmd.com/read/27780829/exposure-to-fine-particulate-air-pollution-is-associated-with-endothelial-injury-and-systemic-inflammation
#16
C A Pope, Aruni Bhatnagar, James McCracken, Wesley T Abplanalp, Daniel J Conklin, Timothy E O'Toole
RATIONALE: Epidemiologic evidence indicates that exposures to fine particulate matter air pollution (PM2.5) contribute to global burden of disease, primarily as a result of increased risk of cardiovascular morbidity and mortality. However, mechanisms by which PM2.5 exposure induces cardiovascular injury remain unclear. PM2.5-induced endothelial dysfunction and systemic inflammation have been implicated, but direct evidence is lacking. OBJECTIVE: To examine whether acute exposure to PM2...
October 25, 2016: Circulation Research
https://www.readbyqxmd.com/read/27777247/amp-activated-protein-kinase-%C3%AE-2-in-neutrophils-regulates-vascular-repair-via-hypoxia-inducible-factor-1%C3%AE-and-a-network-of-proteins-affecting-metabolism-and-apoptosis
#17
Randa Abdel Malik, Nina Zippel, Timo Frömel, Juliana Heidler, Sven Zukunft, Barbara Walzog, Nariman Ansari, Francesco Pampaloni, Susanne Wingert, Michael A Rieger, Ilka Wittig, Beate Fisslthaler, Ingrid Fleming
RATIONALE: The AMP-activated protein kinase (AMPK) is stimulated by hypoxia and while the AMPKα1 catalytic subunit has been implicated in angiogenesis, little is known about the role played by the AMPKα2 subunit in vascular repair. OBJECTIVE: To determine the role of the AMPKα2 subunit in vascular repair. METHODS AND RESULTS: Recovery of blood flow after femoral artery ligation was impaired (>80%) in AMPKα2(-/-) versus wild-type mice, a phenotype reproduced in mice lacking AMPKα2 in myeloid cells (AMPKα2(ΔMC))...
October 24, 2016: Circulation Research
https://www.readbyqxmd.com/read/27765793/a-precision-medicine-approach-to-the-rescue-of-function-on-malignant-calmodulinopathic-long-qt-syndrome
#18
Worawan B Limpitikul, Ivy E Dick, David Tester, Nicole J Boczek, Pattraranee Limphong, Wanjun Yang, Myoung Hyun Choi, Jennifer Babich, Deborah DiSilvestre, Ronald J Kanter, Gordon F Tomaselli, Michael J Ackerman, David Yue
RATIONALE: Calmodulinopathies comprise a new category of potentially life-threatening genetic arrhythmia syndromes capable of producing severe long QT syndrome (LQTS) with mutations involving either CALM1, CALM2, or CALM3 The underlying basis of this form of LQTS is a disruption of Ca(2+)/CaM-dependent inactivation (CDI) of L-type Ca(2+) channels (LTCCs). OBJECTIVE: To gain insight into the mechanistic underpinnings of calmodulinopathies and devise new therapeutic strategies for the treatment of this form of LQTS...
October 20, 2016: Circulation Research
https://www.readbyqxmd.com/read/27756793/microrna-181b-controls-atherosclerosis-and-aneurysms-through-regulation-of-timp-3-and-elastin
#19
Karina Di Gregoli, Nur Najmi Mohamad Anuar, Rosaria Bianco, Stephen J White, Andrew C Newby, Sarah J George, Jason L Johnson
RATIONALE: Atherosclerosis and aneurysms are leading causes of mortality worldwide. MicroRNAs (miRs) are key determinants of gene and protein expression, and atypical miR expression has been associated with a number of cardiovascular diseases; although their contributory role to atherosclerotic plaque and abdominal aortic aneurysm (AAA) stability are poorly understood. OBJECTIVE: To investigate whether miR-181b regulates TIMP-3 expression and affects atherosclerosis and aneurysms Methods and Results: Here, we demonstrate that miR-181b was over-expressed in symptomatic human atherosclerotic plaques and abdominal aortic aneurysms, and correlated with decreased expression of predicted miR-181b targets, TIMP-3 and elastin...
October 18, 2016: Circulation Research
https://www.readbyqxmd.com/read/27756792/a-microrna302-367-erk1-2-klf2-s1pr1-pathway-prevents-tumor-growth-via-restricting-angiogenesis-and-improving-vascular-stability
#20
Jingjiang Pi, Ting Tao, Tao Zhuang, Huimin Sun, Xiaoli Chen, Jie Liu, Yu Cheng, Zuoren Yu, Helen H Zhu, Wei-Qiang Gao, Yuanzhen Suo, Xunbin Wei, Paul Chan, Xiangjian Zheng, Ying Tian, Edward Morrisey, Lin Zhang, Yuzhen Zhang
RATIONALE: Angiogenic hypersprouting and leaky vessels are essential for tumor growth. MicroRNAs have unique therapeutic advantages by targeting multiple pathways of tumor-associated angiogenesis, but the function of individual miRNAs of miR302-367cluster in angiogenesis and tumors has not yet been fully evaluated. OBJECTIVE: To investigate the functions of miR302-367 in developmental angiogenesis and tumor angiogenesis and explore the molecular mechanisms of microRNA for the treatment of pathological neovascularization-related diseases...
October 18, 2016: Circulation Research
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