Full Text Journal Articles by
Author Axel Vater


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Neutralizing Complement C5a Protects Mice with Pneumococcal Pulmonary Sepsis.

Holger Müller-Redetzky, Ute Kellermann, Sandra-Maria Wienhold, Birgitt Gutbier, Jasmin Lienau, Katharina Hellwig, Katrin Reppe, Eleftheria Letsiou, Thomas Tschernig, Markus Scholz, Peter Ahnert, Christian Maasch, Kai Hoehlig, Sven Klussmann, Axel Vater, Theresa C Firsching, Judith Hoppe, Norbert Suttorp, Martin Witzenrath,

BACKGROUND:Community-acquired pneumonia and associated sepsis cause high mortality despite antibiotic treatment. Uncontrolled inflammatory host responses contribute to the unfavorable outcome by driving lung and extrapulmonary organ failure. The complement fragment C5a holds significant proinflammatory functions and is associated with tissue damage in various inflammatory conditions. The authors hypothesized that C5a ... Read more >>

Anesthesiology (Anesthesiology)
[2020, 132(4):795-807]

Cited: 0 times

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C5a Blockade Increases Regulatory T Cell Numbers and Protects Against Microvascular Loss and Epithelial Damage in Mouse Airway Allografts.

Mohammad Afzal Khan, Fatimah Alanazi, Hala Abdalrahman Ahmed, Axel Vater, Abdullah Mohammed Assiri, Dieter Clemens Broering,

Microvascular injury during acute rejection has been associated with massive infiltration of CD4+ T effector cells, and the formation of complement products (C3a and C5a). Regulatory T cells (Tregs) are potent immunosuppressors of the adaptive immune system and have proven sufficient to rescue microvascular impairments. Targeting C5a has been linked ... Read more >>

Front Immunol (Frontiers in immunology)
[2018, 9:1010]

Cited: 0 times

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Effect of a calcitonin gene-related peptide-binding L-RNA aptamer on neuronal activity in the rat spinal trigeminal nucleus.

Michael J M Fischer, Jakob Schmidt, Stanislav Koulchitsky, Sven Klussmann, Axel Vater, Karl Messlinger,

Calcitonin gene-related peptide (CGRP) plays a major role in the pathogenesis of migraine and other primary headaches. Spinal trigeminal neurons integrate nociceptive afferent input from trigeminal tissues including intracranial afferents, and their activity is thought to reflect facial pain and headache in man. CGRP receptor inhibitors and anti-CGRP antibodies have ... Read more >>

J Headache Pain (The Journal of Headache and Pain)
[2018, 19(1):3]

Cited: 1 time

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Signaling of the Complement Cleavage Product Anaphylatoxin C5a Through C5aR (CD88) Contributes to Pharmacological Hematopoietic Stem Cell Mobilization.

Kamila Bujko, Sylwia Rzeszotek, Kai Hoehlig, Jun Yan, Axel Vater, Mariusz Z Ratajczak,

Several mechanisms have been postulated for orchestrating the mobilization of hematopoietic stem/progenitor cells (HSPCs), and we previously proposed that activation of the complement cascade plays a crucial role in the initiation and execution of the egress of HSPCs from bone marrow (BM) into peripheral blood (PB). In support of this ... Read more >>

Stem Cell Rev Rep (Stem cell reviews and reports)
[2017, 13(6):793-800]

Cited: 8 times

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Increasing Tumor-Infiltrating T Cells through Inhibition of CXCL12 with NOX-A12 Synergizes with PD-1 Blockade.

Dirk Zboralski, Kai Hoehlig, Dirk Eulberg, Anna Frömming, Axel Vater,

Immune checkpoint inhibitors promote T cell-mediated killing of cancer cells; however, only a subset of patients benefit from the treatment. A possible reason for this limitation may be that the tumor microenvironment (TME) is immune privileged, which may exclude cytotoxic T cells from the vicinity of cancer cells. The chemokine ... Read more >>

Cancer Immunol Res (Cancer immunology research)
[2017, 5(11):950-956]

Cited: 17 times

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CXCL12/SDF-1-Dependent Retinal Migration of Endogenous Bone Marrow-Derived Stem Cells Improves Visual Function after Pharmacologically Induced Retinal Degeneration.

Volker Enzmann, Stéphanie Lecaudé, Anna Kruschinski, Axel Vater,

Mobilized bone marrow-derived stem cells (BMSC) have been discussed as an alternative strategy for endogenous repair. Thereby, different approaches for BMSC mobilization have been pursued. Herein, the role of a newly discovered oligonucleotide for retinal homing and regeneration capability of BMSCs was investigated in the sodium iodate (NaIO3) model of ... Read more >>

Stem Cell Rev Rep (Stem cell reviews and reports)
[2017, 13(2):278-286]

Cited: 5 times

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Low-Intensity Training and the C5a Complement Antagonist NOX-D21 Rescue the mdx Phenotype through Modulation of Inflammation.

Janek Hyzewicz, Jun Tanihata, Mutsuki Kuraoka, Yuko Nitahara-Kasahara, Teiva Beylier, Urs T Ruegg, Axel Vater, Shin'ichi Takeda,

Inflammatory events occurring in dystrophic muscles contribute to the progression of Duchenne muscular dystrophy (DMD). Low-intensity training (LIT) attenuates the phenotype of mdx mice, an animal model for DMD. Therefore, we postulated that LIT could have anti-inflammatory properties. We assessed levels of inflammatory cytokines and infiltrated immune cells in gastrocnemius ... Read more >>

Am. J. Pathol. (The American journal of pathology)
[2017, 187(5):1147-1161]

Cited: 4 times

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A Combined PD-1/C5a Blockade Synergistically Protects against Lung Cancer Growth and Metastasis.

Daniel Ajona, Sergio Ortiz-Espinosa, Haritz Moreno, Teresa Lozano, María J Pajares, Jackeline Agorreta, Cristina Bértolo, Juan J Lasarte, Silvestre Vicent, Kai Hoehlig, Axel Vater, Fernando Lecanda, Luis M Montuenga, Ruben Pio,

Disruption of the programmed cell death protein 1 (PD-1) pathway with immune checkpoint inhibitors represents a major breakthrough in the treatment of non-small cell lung cancer. We hypothesized that combined inhibition of C5a/C5aR1 and PD-1 signaling may have a synergistic antitumor effect. The RMP1-14 antibody was used to block PD-1, ... Read more >>

Cancer Discov (Cancer discovery)
[2017, 7(7):694-703]

Cited: 32 times

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Complement system modulation as a target for treatment of arrhythmogenic cardiomyopathy.

Manolis Mavroidis, Constantinos H Davos, Stelios Psarras, Aimilia Varela, Nikolaos C Athanasiadis, Michalis Katsimpoulas, Ioanna Kostavasili, Christian Maasch, Axel Vater, J Peter van Tintelen, Yassemi Capetanaki,

Inflammation may contribute to disease progression in arrhythmogenic cardiomyopathy (ACM). However, its role in this process is unresolved. Our goal was to delineate the pathogenic role of the complement system in a new animal model of ACM and in human disease. Using cardiac histology, echocardiography, and electrocardiography, we have demonstrated ... Read more >>

Basic Res. Cardiol. (Basic research in cardiology)
[2015, 110(3):27]

Cited: 12 times

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Intravitreal inhibition of complement C5a reduces choroidal neovascularization in mice.

Claudia Brockmann, Tobias Brockmann, Sabrina Dege, Catharina Busch, Norbert Kociok, Axel Vater, Sven Klussmann, Olaf Strauß, Antonia M Joussen,

To investigate the influence of complement component C5a inhibition on laser-induced choroidal neovascularization (CNV) in mice using a C5a specific L-aptamer.In C57BL/6 J mice CNV was induced by argon-laser, C5a-inhibitor (NOX-D20) was intravitreally injected in three concentrations: 0.3, 3.0, and 30 mg/ml. The unPEGylated derivate (NOX-D20001) was applied at 3.0 ... Read more >>

Graefes Arch. Clin. Exp. Ophthalmol. (Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie)
[2015, 253(10):1695-1704]

Cited: 7 times

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Structural basis for the targeting of complement anaphylatoxin C5a using a mixed L-RNA/L-DNA aptamer.

Laure Yatime, Christian Maasch, Kai Hoehlig, Sven Klussmann, Gregers R Andersen, Axel Vater,

L-Oligonucleotide aptamers (Spiegelmers) consist of non-natural L-configured nucleotides and are of particular therapeutic interest due to their high resistance to plasma nucleases. The anaphylatoxin C5a, a potent inflammatory mediator generated during complement activation that has been implicated with organ damage, can be efficiently targeted by Spiegelmers. Here, we present the ... Read more >>

Nat Commun (Nature communications)
[2015, 6:6481]

Cited: 20 times

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Turning mirror-image oligonucleotides into drugs: the evolution of Spiegelmer(®) therapeutics.

Axel Vater, Sven Klussmann,

Spiegelmers are synthetic target-binding oligonucleotides built from non-natural l-nucleotides. Like aptamers, Spiegelmers fold into distinct shapes that bind the targets with high affinity and selectivity. Furthermore, the mirror-image configuration confers plasma stability and immunological passivity. Various Spiegelmers against pharmacologically attractive targets were shown to be efficacious in animal models. Three ... Read more >>

Drug Discov. Today (Drug discovery today)
[2015, 20(1):147-155]

Cited: 43 times

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Identification and characterization of a mirror-image oligonucleotide that binds and neutralizes sphingosine 1-phosphate, a central mediator of angiogenesis.

Werner G Purschke, Kai Hoehlig, Klaus Buchner, Dirk Zboralski, Frank Schwoebel, Axel Vater, Sven Klussmann,

The sphingolipid S1P (sphingosine 1-phosphate) is known to be involved in a number of pathophysiological conditions such as cancer, autoimmune diseases and fibrosis. It acts extracellularly through a set of five G-protein-coupled receptors, but its intracellular actions are also well documented. Employing in vitro selection techniques, we identified an L-aptamer (Spiegelmer®) ... Read more >>

Biochem. J. (The Biochemical journal)
[2014, 462(1):153-162]

Cited: 9 times

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SDF-1 inhibition targets the bone marrow niche for cancer therapy.

Aldo M Roccaro, Antonio Sacco, Werner G Purschke, Michele Moschetta, Klaus Buchner, Christian Maasch, Dirk Zboralski, Stefan Zöllner, Stefan Vonhoff, Yuji Mishima, Patricia Maiso, Michaela R Reagan, Silvia Lonardi, Marco Ungari, Fabio Facchetti, Dirk Eulberg, Anna Kruschinski, Axel Vater, Giuseppe Rossi, Sven Klussmann, Irene M Ghobrial,

Bone marrow (BM) metastasis remains one of the main causes of death associated with solid tumors as well as multiple myeloma (MM). Targeting the BM niche to prevent or modulate metastasis has not been successful to date. Here, we show that stromal cell-derived factor-1 (SDF-1/CXCL12) is highly expressed in active ... Read more >>

Cell Rep (Cell reports)
[2014, 9(1):118-128]

Cited: 40 times

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In vivo therapy monitoring of experimental rheumatoid arthritis in rats using near-infrared fluorescence imaging.

Sonja Vollmer, Ines Gemeinhardt, Axel Vater, Beatrix Schnorr, Jörg Schnorr, Jan Voigt, Bernd Ebert,

An in vivo near-infrared fluorescence (NIRF) imaging technique is described for therapy monitoring of ankle joints affected by collagen-induced arthritis, a model of human rheumatoid arthritis. Arthritis was induced in rats by intradermal injections of collagen and Freund's incomplete adjuvant. For in vivo imaging, the nonspecific NIR dye tetrasulfocyanine (TSC) ... Read more >>

J Biomed Opt (Journal of biomedical optics)
[2014, 19(3):36011]

Cited: 0 times

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Peripherally circulating ghrelin does not mediate alcohol-induced reward and alcohol intake in rodents.

Elisabet Jerlhag, Lisa Ivanoff, Axel Vater, Jörgen A Engel,

BACKGROUND: Development of alcohol dependence, a chronic and relapsing disease, largely depends on the effects of alcohol on the brain reward systems. By elucidating the mechanisms involved in alcohol use disorder, novel treatment strategies may be developed. Ghrelin, the endogenous ligand for the growth hormone secretagogue receptor 1A, acts as ... Read more >>

Alcohol. Clin. Exp. Res. (Alcoholism, clinical and experimental research)
[2014, 38(4):959-968]

Cited: 15 times

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A mixed mirror-image DNA/RNA aptamer inhibits glucagon and acutely improves glucose tolerance in models of type 1 and type 2 diabetes.

Axel Vater, Simone Sell, Przemyslaw Kaczmarek, Christian Maasch, Klaus Buchner, Ewa Pruszynska-Oszmalek, Pawel Kolodziejski, Werner G Purschke, Krzysztof W Nowak, Mathias Z Strowski, Sven Klussmann,

Excessive secretion of glucagon, a functional insulin antagonist, significantly contributes to hyperglycemia in type 1 and type 2 diabetes. Accordingly, immunoneutralization of glucagon or genetic deletion of the glucagon receptor improved glucose homeostasis in animal models of diabetes. Despite this strong evidence, agents that selectively interfere with endogenous glucagon have ... Read more >>

J. Biol. Chem. (The Journal of biological chemistry)
[2013, 288(29):21136-21147]

Cited: 29 times

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Immune and inflammatory cell involvement in the pathology of idiopathic pulmonary arterial hypertension.

Rajkumar Savai, Soni S Pullamsetti, Julia Kolbe, Ewa Bieniek, Robert Voswinckel, Ludger Fink, Axel Scheed, Christin Ritter, Bhola K Dahal, Axel Vater, Sven Klussmann, Hossein A Ghofrani, Norbert Weissmann, Walter Klepetko, Gamal A Banat, Werner Seeger, Friedrich Grimminger, Ralph T Schermuly,

RATIONALE: Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction and vascular remodeling. Recent studies have revealed that immune and inflammatory responses play a crucial role in pathogenesis of idiopathic PAH. OBJECTIVES: To systematically evaluate the number and cross-sectional distribution of inflammatory cells in different sizes of pulmonary arteries from explanted ... Read more >>

Am. J. Respir. Crit. Care Med. (American journal of respiratory and critical care medicine)
[2012, 186(9):897-908]

Cited: 103 times

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Dual blockade of the homeostatic chemokine CXCL12 and the proinflammatory chemokine CCL2 has additive protective effects on diabetic kidney disease.

Murthy N Darisipudi, Onkar P Kulkarni, Sufyan G Sayyed, Mi Ryu, Adriana Migliorini, Costanza Sagrinati, Eliana Parente, Axel Vater, Dirk Eulberg, Sven Klussmann, Paola Romagnani, Hans-Joachim Anders,

Monocyte/ chemoattractant protein-1/chemokine ligand (CCL) 2 and stromal cell-derived factor-1/CXCL12 both contribute to glomerulosclerosis in mice with type 2 diabetes mellitus, through different mechanisms. CCL2 mediates macrophage-related inflammation, whereas CXCL12 contributes to podocyte loss. Therefore, we hypothesized that dual antagonism of these chemokines might have additive protective effects on the ... Read more >>

Am. J. Pathol. (The American journal of pathology)
[2011, 179(1):116-124]

Cited: 53 times

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Polyetheylenimine-polyplexes of Spiegelmer NOX-A50 directed against intracellular high mobility group protein A1 (HMGA1) reduce tumor growth in vivo.

Christian Maasch, Axel Vater, Klaus Buchner, Werner G Purschke, Dirk Eulberg, Stefan Vonhoff, Sven Klussmann,

High mobility group A1 (HMGA1) proteins belong to a group of architectural transcription factors that are overexpressed in a range of human malignancies, including pancreatic adenocarcinoma. They promote anchorage-independent growth and epithelial-mesenchymal transition and are therefore suggested as potential therapeutic targets. Employing in vitro selection techniques against a chosen fragment ... Read more >>

J. Biol. Chem. (The Journal of biological chemistry)
[2010, 285(51):40012-40018]

Cited: 18 times

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Extra domain B fibronectin as a target for near-infrared fluorescence imaging of rheumatoid arthritis affected joints in vivo.

Sonja Vollmer, Axel Vater, Kai Licha, Ines Gemeinhardt, Ole Gemeinhardt, Jan Voigt, Bernd Ebert, Jörg Schnorr, Matthias Taupitz, Rainer Macdonald, Michael Schirner,

Abstract We investigated a molecular imaging approach for the detection of collagen-induced arthritis in rats by targeting the extra domain B (ED-B) of the extracellular matrix protein fibronectin. ED-B is a highly conserved domain (identical in human and rats) that is produced by alternative splicing during embryonic development and during ... Read more >>

Mol Imaging (Molecular imaging)
[2009, 8(6):330-340]

Cited: 7 times

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Novel use of enantiomer


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Inhibition of stimulated meningeal blood flow by a calcitonin gene-related peptide binding mirror-image RNA oligonucleotide.

Thomas Denekas, Markus Tröltzsch, Axel Vater, Sven Klussmann, Karl Messlinger,

Calcitonin gene-related peptide (CGRP) released from trigeminal afferents is known to play an important role in the control of intracranial blood flow. In a rat preparation with exposed cranial dura mater, periods of electrical stimulation induce increases in meningeal blood flow. These responses are due to arterial vasodilatation mediated in ... Read more >>

Br. J. Pharmacol. (British journal of pharmacology)
[2006, 148(4):536-543]

Cited: 21 times

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Vasopressin-binding l-nucleic acid


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Variable sensitivity to noxious heat is mediated by differential expression of the CGRP gene.

Jeffrey S Mogil, Frank Miermeister, Frank Seifert, Kate Strasburg, Katharina Zimmermann, Heiko Reinold, Jean-Sebastien Austin, Nadia Bernardini, Elissa J Chesler, Heiko A Hofmann, Christian Hordo, Karl Messlinger, Kumar V S Nemmani, Andrew L Rankin, Jennifer Ritchie, Angela Siegling, Shad B Smith, Susana Sotocinal, Axel Vater, Sonya G Lehto, Sven Klussmann, Remi Quirion, Martin Michaelis, Marshall Devor, Peter W Reeh,

Heat sensitivity shows considerable functional variability in humans and laboratory animals, and is fundamental to inflammatory and possibly neuropathic pain. In the mouse, at least, much of this variability is genetic because inbred strains differ robustly in their behavioral sensitivity to noxious heat. These strain differences are shown here to ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2005, 102(36):12938-12943]

Cited: 96 times

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