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101. Methods for the identification and characterization of extracellular vesicles in cardiovascular studies: from exosomes to microvesicles

Author

Davidson, Sean M., primary, Boulanger, Chantal M., additional, Aikawa, Elena, additional, Badimon, Lina, additional, Barile, Lucio, additional, Binder, Christoph J., additional, Brisson, Alain, additional, Buzas, Edit, additional, Emanueli, Costanza, additional, Jansen, Felix, additional, Katsur, Miroslava, additional, Lacroix, Romaric, additional, Lim, Sai Kiang, additional, Mackman, Nigel, additional, Mayr, Manuel, additional, Menasché, Philippe, additional, Nieuwland, Rienk, additional, Sahoo, Susmita, additional, Takov, Kaloyan, additional, Thum, Thomas, additional, Vader, Pieter, additional, Wauben, Marca H.M., additional, Witwer, Kenneth, additional, and Sluijter, Joost P.G., additional

Published
2022
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102. A neutrophil - B-cell axis governs disease tolerance during sepsis via Cxcr4

Author

Gawish, Riem, primary, Maier, Barbara B., additional, Obermayer, Georg, additional, Watzenböck, Martin L., additional, Gorki, Anna-Dorothea, additional, Quattrone, Federica, additional, Farhat, Asma, additional, Lakovits, Karin, additional, Hladik, Anastasiya, additional, Korosec, Ana, additional, Alimohammadi, Arman, additional, Mesteri, Ildiko, additional, Oberndorfer, Felicitas, additional, Oakley, Fiona, additional, Brain, John, additional, Boon, Louis, additional, Lang, Irene, additional, Binder, Christoph J., additional, and Knapp, Sylvia, additional

Published
2022
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103. Nonalcoholic Fatty Liver Disease

Author

Ding, Lingling, Oligschlaeger, Yvonne, Shiri-Sverdlov, Ronit, Houben, Tom, von Eckardstein, Arnold, Binder, Christoph J., Molecular Genetics, and RS: NUTRIM - R2 - Liver and digestive health

Subjects
0301 basic medicine, medicine.medical_specialty, business.industry, nutritional and metabolic diseases, Treatment options, medicine.disease, Bioinformatics, digestive system, digestive system diseases, 3. Good health, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease/drug therapy, Nonalcoholic fatty liver disease, Epidemiology, medicine, Humans, Metabolic Syndrome/epidemiology, 030211 gastroenterology & hepatology, Metabolic syndrome, Metabolic disease, business
Abstract

Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of the metabolic syndrome (MetS) and comprises one of the largest health threats of the twenty-first century. In this chapter, we review the current state of knowledge of NAFLD and underline the striking similarities with atherosclerosis. We first describe current epidemiological data showing the staggering increase of NAFLD numbers and its related clinical and economic costs. We then provide an overview of pathophysiological hepatic processes in NAFLD and highlight the systemic aspects of NAFLD that point toward metabolic crosstalk between organs as an important cause of metabolic disease. Finally, we end by highlighting the currently investigated therapeutic approaches for NAFLD, which also show strong similarities with a range of treatment options for atherosclerosis.

Published
2022

104. The Comparability of Anti-Spike SARS-CoV-2 Antibody Tests is Time-Dependent: a Prospective Observational Study

Author

Perkmann, Thomas, primary, Mucher, Patrick, additional, Perkmann-Nagele, Nicole, additional, Radakovics, Astrid, additional, Repl, Manuela, additional, Koller, Thomas, additional, Schmetterer, Klaus G., additional, Bigenzahn, Johannes W., additional, Leitner, Florentina, additional, Jordakieva, Galateja, additional, Wagner, Oswald F., additional, Binder, Christoph J., additional, and Haslacher, Helmuth, additional

Published
2022
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105. IFNγ-Stimulated B Cells Inhibit T Follicular Helper Cells and Protect Against Atherosclerosis

Author

Douna, Hidde, primary, de Mol, J., additional, Amersfoort, Jacob, additional, Schaftenaar, Frank H., additional, Kiss, Mate G., additional, Suur, Bianca E., additional, Kroner, Mara J., additional, Binder, Christoph J., additional, Bot, Ilze, additional, Van Puijvelde, Gijs H. M., additional, Kuiper, Johan, additional, and Foks, Amanda C., additional

Published
2022
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106. Comparison of the Prevalence of SARS-CoV-2 Nucleoprotein Antibodies in Healthcare Workers and an Unselected Adult and Pediatric All-Comer Patient Population in Austria

Author

Riesenhuber, Martin, primary, Nitsche, Christian, additional, Binder, Christoph J., additional, Schernhammer, Eva S., additional, Stamm, Tanja A., additional, Jakse, Friedrich, additional, Anwari, Elaaha, additional, Hamidi, Fardin, additional, Haslacher, Helmuth, additional, Perkmann, Thomas, additional, Hengstenberg, Christian, additional, and Zelniker, Thomas A., additional

Published
2022
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107. Comparison of Five Anti-SARS-CoV-2 Antibody Assays Across Three Doses of BNT162b2 Reveals Insufficient Standardization of SARS-CoV-2 Serology

Author

Perkmann, Thomas, primary, Mucher, Patrick, additional, Ösze, Darlene, additional, Müller, Antonia, additional, Perkmann-Nagele, Nicole, additional, Koller, Thomas, additional, Radakovics, Astrid, additional, Flieder, Ines, additional, Repl, Manuela, additional, Marculescu, Rodrig, additional, Wolzt, Michael, additional, Wagner, Oswald F., additional, Binder, Christoph J., additional, and Haslacher, Helmuth, additional

Published
2022
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108. Mitochondrial C5aR1 activity in macrophages controls IL-1β production underlying sterile inflammation

Author

Niyonzima, Nathalie, primary, Rahman, Jubayer, additional, Kunz, Natalia, additional, West, Erin E., additional, Freiwald, Tilo, additional, Desai, Jigar V., additional, Merle, Nicolas S., additional, Gidon, Alexandre, additional, Sporsheim, Bjørnar, additional, Lionakis, Michail S., additional, Evensen, Kristin, additional, Lindberg, Beate, additional, Skagen, Karolina, additional, Skjelland, Mona, additional, Singh, Parul, additional, Haug, Markus, additional, Ruseva, Marieta M., additional, Kolev, Martin, additional, Bibby, Jack, additional, Marshall, Olivia, additional, O’Brien, Brett, additional, Deeks, Nigel, additional, Afzali, Behdad, additional, Clark, Richard J., additional, Woodruff, Trent M., additional, Pryor, Milton, additional, Yang, Zhi-Hong, additional, Remaley, Alan T., additional, Mollnes, Tom E., additional, Hewitt, Stephen M., additional, Yan, Bingyu, additional, Kazemian, Majid, additional, Kiss, Máté G., additional, Binder, Christoph J., additional, Halvorsen, Bente, additional, Espevik, Terje, additional, and Kemper, Claudia, additional

Published
2021
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109. Impact of Specific N-Glycan Modifications on the Use of Plant-Produced SARS-CoV-2 Antigens in Serological Assays

Author

Schwestka, Jennifer, König-Beihammer, Julia, Shin, Yun-Ji, Vavra, Ulrike, Kienzl, Nikolaus F., Grünwald-Gruber, Clemens, Maresch, Daniel, Klausberger, Miriam, Laurent, Elisabeth, Stadler, Maria, Manhart, Gabriele, Huber, Jasmin, Hofner, Manuela, Vierlinger, Klemens, Weinhäusel, Andreas, Swoboda, Ines, Binder, Christoph J., Gerner, Wilhelm, Grebien, Florian, Altmann, Friedrich, Mach, Lukas, Stöger, Eva, and Strasser, Richard

Subjects
Plant Science
Published
2021
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111. Preanalytical stability of SARS-CoV-2 anti-nucleocapsid antibodies.

Author

Niedrist, Tobias, Kriegl, Lisa, Zurl, Christoph J., Schmidt, Felix, Perkmann-Nagele, Nicole, Mucher, Patrick, Repl, Manuela, Flieder, Ines, Radakovics, Astrid, Sieghart, Daniela, Radner, Helga, Aletaha, Daniel, Binder, Christoph J., Gülly, Christian, Krause, Robert, Herrmann, Markus, Wagner, Oswald F., Perkmann, Thomas, and Haslacher, Helmuth

Subjects
SARS-CoV-2, IMMUNOGLOBULINS, ELECTROCHEMILUMINESCENCE
Abstract

Anti-nucleocapsid (NC) antibodies are produced in response to SARS-CoV-2 infection. Therefore, they are well suited for the detection of a previous infection. Especially in the case of seroprevalence studies or during the evaluation of a novel in-vitro diagnostic test, samples have been stored at <−70 °C (short- and long-term) or 2–10 °C (short-term) before analysis. This study aimed to assess the impact of different storage conditions relevant to routine biobanking on anti-NC antibodies. The preanalytical impact of short-term storage (84 [58–98] days) on <−70 °C and for 14 days at 2–10 °C was evaluated using samples from 111 donors of the MedUni Vienna Biobank. Long-term effects (443 [409–468] days) were assessed using 208 samples from Biobank Graz and 49 samples from Biobank Vienna. Anti-Nucleocapsid antibodies were measured employing electrochemiluminescence assays (Roche Anti-SARS-CoV-2). After short-term storage, the observed changes did not exceed the extent that could be explained by analytical variability. In contrast, results after long-term storage were approximately 20% higher and seemed to increase with storage duration. This effect was independent of the biobank from which the samples were obtained. Accordingly, the sensitivity increased from 92.6 to 95.3% (p=0.008). However, comparisons with data from Anti-Spike protein assays, where these deviations were not apparent, suggest that this deviation could also be explained by the analytical variability of the qualitative Anti-NC assay. Results from anti-NC antibodies are stable during short-term storage at <−70 °C and 2–10 °C. After long-term storage, a slight increase in sensitivity could not be ruled out. [ABSTRACT FROM AUTHOR]

Published
2023
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115. The comparability of Anti-Spike SARS-CoV-2 antibody tests is time-dependent: a prospective observational study

Author

Perkmann, Thomas, primary, Mucher, Patrick, additional, Perkmann-Nagele, Nicole, additional, Radakovics, Astrid, additional, Repl, Manuela, additional, Koller, Thomas, additional, Schmetterer, Klaus G, additional, Bigenzahn, Johannes W, additional, Leitner, Florentina, additional, Jordakieva, Galateja, additional, Wagner, Oswald F, additional, Binder, Christoph J, additional, and Haslacher, Helmuth, additional

Published
2021
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116. Spike Protein Antibodies Mediate the Apparent Correlation between SARS-CoV-2 Nucleocapsid Antibodies and Neutralization Test Results

Author

Perkmann, Thomas, primary, Koller, Thomas, additional, Perkmann-Nagele, Nicole, additional, Klausberger, Miriam, additional, Duerkop, Mark, additional, Holzer, Barbara, additional, Hartmann, Boris, additional, Mucher, Patrick, additional, Radakovics, Astrid, additional, Ozsvar-Kozma, Maria, additional, Wagner, Oswald F., additional, Binder, Christoph J., additional, and Haslacher, Helmuth, additional

Published
2021
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118. Abstract 101: B1b Cell Homeostasis Is Maintained By Cd40 In Atherosclerosis

Author

Reiche, Myrthe E, primary, Pattarabajinard, Oom, additional, Upadhye, Aditi, additional, Poels, Kikkie, additional, van Tiel, Claudia, additional, Malin, Stephen G, additional, Binder, Christoph J, additional, Gerdes, Norbert, additional, Weber, Christian, additional, Atzler, Dorothee, additional, McNamara, Coleen A, additional, and Lutgens, Esther, additional

Published
2021
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120. Publisher Correction: Oxidized phospholipids are proinflammatory and proatherogenic in hypercholesterolaemic mice

Author

Que, Xuchu, Hung, Ming-Yow, Yeang, Calvin, Gonen, Ayelet, Prohaska, Thomas A., Sun, Xiaoli, Diehl, Cody, Määttä, Antti, Gaddis, Dalia E., Bowden, Karen, Pattison, Jennifer, MacDonald, Jeffrey G., Ylä-Herttuala, Seppo, Mellon, Pamela L., Hedrick, Catherine C., Ley, Klaus, Miller, Yury I., Glass, Christopher K., Peterson, Kirk L., Binder, Christoph J., Tsimikas, Sotirios, and Witztum, Joseph L.

Published
2018
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122. Tetrahydroxylated bile acids improve cholestatic liver and bile duct injury in the Mdr2−/− mouse model of sclerosing cholangitis via immunomodulatory effects.

Author

Fuchs, Claudia D., Dixon, Emmanuel D., Hendrikx, Tim, Mlitz, Veronika, Wahlström, Annika, Ståhlman, Marcus, Scharnagl, Hubert, Stojakovic, Tatjana, Binder, Christoph J., Marschall, Hanns‐Ulrich, and Trauner, Michael

Subjects
LIQUID chromatography-mass spectrometry, BILE ducts, BILE acids, LABORATORY mice, CHOLANGITIS
Abstract

Bile salt export pump (Bsep) (Abcb11)−/− mice are protected from acquired cholestatic injury due to metabolic preconditioning with a hydrophilic bile acid (BA) pool with formation of tetrahydroxylated bile acids (THBAs). We aimed to explore whether loss of Bsep and subsequent elevation of THBA levels may have immunomodulatory effects, thus improving liver injury in the multidrug resistance protein 2 (Mdr2) (Abcb4)−/− mouse. Cholestatic liver injury in Mdr2−/−Bsep−/− double knockout (DKO), Mdr2−/−, Bsep−/−, and wild‐type mice was studied for comparison. Mdr2−/− mice were treated with a THBA (3α,6α,7α,12α‐Tetrahydroxycholanoic acid). RNA/protein expression of inflammatory/fibrotic markers were investigated. Serum BA‐profiling was assessed by ultra‐performance liquid chromatography tandem mass spectrometry. Hepatic immune cell profile was quantified by flow cytometric analysis (FACS). In vitro, the THBA effect on chenodeoxycholic acid (CDCA)–induced inflammatory signaling in hepatocyte and cholangiocytes as well as lipopolysaccharide (LPS)/interferon‐γ (IFN‐γ)–induced macrophage activation was analyzed. In contrast to Mdr2−/−, DKO mice showed no features of sclerosing cholangitis. Sixty‐seven percent of serum BAs in DKO mice were polyhydroxylated (mostly THBAs), whereas Mdr2−/− mice did not have these BAs. Compared with Mdr2−/−, DKO animals were protected from hepatic inflammation/fibrosis. THBA feeding in Mdr2−/− mice improved liver injury. FACS analysis in DKO and Mdr2−/− THBA‐fed mice showed changes of the hepatic immune cell profile towards an anti‐inflammatory pattern. Early growth response 1 (EGR1) protein expression was reduced in DKO and in Mdr2−/− THBA‐fed mice compared with Mdr2−/− control mice. In vitro, THBA‐reduced CDCA induced EGR1 protein and mRNA expression of inflammatory markers in hepatocytes and cholangiocytes. LPS/IFN‐γ–induced macrophage activation was ameliorated by THBA. THBAs repress EGR1‐related key pro‐inflammatory pathways. Conclusion: THBA and their downstream targets may represent a potential treatment strategy for cholestatic liver diseases. [ABSTRACT FROM AUTHOR]

Published
2022
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123. WAVE1 mediates suppression of phagocytosis by phospholipid-derived DAMPs

Author

Matt, Ulrich, Sharif, Omar, Martins, Rui, Furtner, Tanja, Langeberg, Lorene, Gawish, Riem, Elbau, Immanuel, Zivkovic, Ana, Lakovits, Karin, Oskolkova, Olga, Doninger, Bianca, Vychytil, Andreas, Perkmann, Thomas, Schabbauer, Gernot, Binder, Christoph J., Bochkov, Valery N., Scott, John D., and Knapp, Sylvia

Subjects
Binding proteins -- Health aspects, Immune response -- Research, Phagocytosis -- Research, Health care industry
Abstract

Clearance of invading pathogens is essential to preventing overwhelming inflammation and sepsis that are symptomatic of bacterial peritonitis. Macrophages participate in this innate immune response by engulfing and digesting pathogens, [...]

Published
2013
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124. Adaptive immunity in atherogenesis: new insights and therapeutic approaches

Author

Lichtman, Andrew H., Binder, Christoph J., Tsimikas, Sotirios, and Witztum, Joseph L.

Subjects
Inflammation -- Research, Immunity -- Research, Atherosclerosis -- Research, Health care industry
Abstract

Many remarkable advances have improved our understanding of the cellular and molecular events in the pathogenesis of atherosclerosis. Chief among these is the accumulating knowledge of how the immune system [...]

Published
2013
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126. Pharmacological inhibition of fatty acid oxidation reduces atherosclerosis progression by suppression of macrophage NLRP3 inflammasome activation

Author

Hohensinner, Philipp J., primary, Lenz, Max, additional, Haider, Patrick, additional, Mayer, Julia, additional, Richter, Manuela, additional, Kaun, Christoph, additional, Goederle, Laura, additional, Brekalo, Mira, additional, Salzmann, Manuel, additional, Sharma, Smriti, additional, Fischer, Michael B., additional, Stojkovic, Stefan, additional, Ramsmayer, Daniel, additional, Hengstenberg, Christian, additional, Podesser, Bruno K., additional, Huber, Kurt, additional, Binder, Christoph J., additional, Wojta, Johann, additional, and Speidl, Walter S., additional

Published
2021
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129. The year 2020 in Atherosclerosis

Author

Binder, Christoph J., primary, Borén, Jan, additional, Catapano, Alberico, additional, Kronenberg, Florian, additional, Mallat, Ziad, additional, Negrini, Simona, additional, Öörni, Katariina, additional, Raggi, Paolo, additional, and von Eckardstein, Arnold, additional

Published
2021
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130. Lipid-lowering and anti-thrombotic therapy in patients with peripheral arterial disease: European Atherosclerosis Society/European Society of Vascular Medicine Joint Statement

Author

Belch, Jill J F, Brodmann, Marianne, Baumgartner, Iris, Binder, Christoph J, Casula, Manuela, Heiss, Christian, Kahan, Thomas, Parini, Paolo, Poredos, Pavel, Catapano, Alberico L, and Tokg��zo��lu, Lale

Subjects
610 Medicine & health
Abstract

Patients with peripheral arterial disease (PAD) are at very high risk of cardiovascular events, but risk factor management is usually suboptimal. This Joint Task Force from the European Atherosclerosis Society and the European Society of Vascular Medicine has updated evidence on the management on dyslipidaemia and thrombotic factors in patients with PAD. Guidelines recommend a low-density lipoprotein cholesterol (LDLC) goal of more than 50% reduction from baseline and

Published
2021
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131. Global perspective of familial hypercholesterolaemia:a cross-sectional study from the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)

Author

Vallejo-Vaz, Antonio J., Stevens, Christophe A.T., Lyons, Alexander R.M., Dharmayat, Kanika I., Freiberger, Tomas, Hovingh, G. Kees, Mata, Pedro, Raal, Frederick J., Santos, Raul D., Soran, Handrean, Watts, Gerald F., Abifadel, Marianne, Aguilar-Salinas, Carlos A., Alhabib, Khalid F., Alkhnifsawi, Mutaz, Almahmeed, Wael, Alnouri, Fahad, Alonso, Rodrigo, Al-Rasadi, Khalid, Al-Sarraf, Ahmad, Al-Sayed, Nasreen, Araujo, Francisco, Ashavaid, Tester F., Banach, Maciej, Béliard, Sophie, Benn, Marianne, Binder, Christoph J., Bogsrud, Martin P., Bourbon, Mafalda, Chlebus, Krzysztof, Corral, Pablo, Davletov, Kairat, Descamps, Olivier S., Durst, Ronen, Ezhov, Marat, Gaita, Dan, Genest, Jacques, Groselj, Urh, Harada-Shiba, Mariko, Holven, Kirsten B., Kayikcioglu, Meral, Khovidhunkit, Weerapan, Lalic, Katarina, Latkovskis, Gustavs, Laufs, Ulrich, Liberopoulos, Evangelos, Lima-Martinez, Marcos M., Nordestgaard, Børge G., Tybjærg-Hansen, Anne, Chen, Yan, Vallejo-Vaz, Antonio J., Stevens, Christophe A.T., Lyons, Alexander R.M., Dharmayat, Kanika I., Freiberger, Tomas, Hovingh, G. Kees, Mata, Pedro, Raal, Frederick J., Santos, Raul D., Soran, Handrean, Watts, Gerald F., Abifadel, Marianne, Aguilar-Salinas, Carlos A., Alhabib, Khalid F., Alkhnifsawi, Mutaz, Almahmeed, Wael, Alnouri, Fahad, Alonso, Rodrigo, Al-Rasadi, Khalid, Al-Sarraf, Ahmad, Al-Sayed, Nasreen, Araujo, Francisco, Ashavaid, Tester F., Banach, Maciej, Béliard, Sophie, Benn, Marianne, Binder, Christoph J., Bogsrud, Martin P., Bourbon, Mafalda, Chlebus, Krzysztof, Corral, Pablo, Davletov, Kairat, Descamps, Olivier S., Durst, Ronen, Ezhov, Marat, Gaita, Dan, Genest, Jacques, Groselj, Urh, Harada-Shiba, Mariko, Holven, Kirsten B., Kayikcioglu, Meral, Khovidhunkit, Weerapan, Lalic, Katarina, Latkovskis, Gustavs, Laufs, Ulrich, Liberopoulos, Evangelos, Lima-Martinez, Marcos M., Nordestgaard, Børge G., Tybjærg-Hansen, Anne, and Chen, Yan

Abstract

Background: The European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (FHSC) global registry provides a platform for the global surveillance of familial hypercholesterolaemia through harmonisation and pooling of multinational data. In this study, we aimed to characterise the adult population with heterozygous familial hypercholesterolaemia and described how it is detected and managed globally. Methods: Using FHSC global registry data, we did a cross-sectional assessment of adults (aged 18 years or older) with a clinical or genetic diagnosis of probable or definite heterozygous familial hypercholesterolaemia at the time they were entered into the registries. Data were assessed overall and by WHO regions, sex, and index versus non-index cases. Findings: Of the 61 612 individuals in the registry, 42 167 adults (21 999 [53·6%] women) from 56 countries were included in the study. Of these, 31 798 (75·4%) were diagnosed with the Dutch Lipid Clinic Network criteria, and 35 490 (84·2%) were from the WHO region of Europe. Median age of participants at entry in the registry was 46·2 years (IQR 34·3–58·0); median age at diagnosis of familial hypercholesterolaemia was 44·4 years (32·5–56·5), with 40·2% of participants younger than 40 years when diagnosed. Prevalence of cardiovascular risk factors increased progressively with age and varied by WHO region. Prevalence of coronary disease was 17·4% (2·1% for stroke and 5·2% for peripheral artery disease), increasing with concentrations of untreated LDL cholesterol, and was about two times lower in women than in men. Among patients receiving lipid-lowering medications, 16 803 (81·1%) were receiving statins and 3691 (21·2%) were on combination therapy, with greater use of more potent lipid-lowering medication in men than in women. Median LDL cholesterol was 5·43 mmol/L (IQR 4·32–6·72) among patients not taking lipid-lowering medications and 4·23 mmol/L (3·20–5·66) among those taking them. Among pati

Published
2021

132. Taking action:European Atherosclerosis Society targets the United Nations Sustainable Development Goals 2030 agenda to fight atherosclerotic cardiovascular disease in Europe

Author

Parini, Paolo, Frikke-Schmidt, Ruth, Tselepis, Alexandros D., Moulin, Philippe, von Eckardstein, Arnold, Binder, Christoph J., Catapano, Alberico L., Ray, Kausik K., Tokgözoğlu, Lale, Parini, Paolo, Frikke-Schmidt, Ruth, Tselepis, Alexandros D., Moulin, Philippe, von Eckardstein, Arnold, Binder, Christoph J., Catapano, Alberico L., Ray, Kausik K., and Tokgözoğlu, Lale

Published
2021

133. APRIL limits atherosclerosis by binding to heparan sulfate proteoglycans

Author

Centraal Diagnostisch Laboratorium, Circulatory Health, Tsiantoulas, Dimitrios, Eslami, Mahya, Obermayer, Georg, Clement, Marc, Smeets, Diede, Mayer, Florian J, Kiss, Máté G, Enders, Lennart, Weißer, Juliane, Göderle, Laura, Lambert, Jordi, Frommlet, Florian, Mueller, André, Hendrikx, Tim, Ozsvar-Kozma, Maria, Porsch, Florentina, Willen, Laure, Afonyushkin, Taras, Murphy, Jane E, Fogelstrand, Per, Donzé, Olivier, Pasterkamp, Gerard, Hoke, Matthias, Kubicek, Stefan, Jørgensen, Helle F, Danchin, Nicolas, Simon, Tabassome, Scharnagl, Hubert, März, Winfried, Borén, Jan, Hess, Henry, Mallat, Ziad, Schneider, Pascal, Binder, Christoph J, Centraal Diagnostisch Laboratorium, Circulatory Health, Tsiantoulas, Dimitrios, Eslami, Mahya, Obermayer, Georg, Clement, Marc, Smeets, Diede, Mayer, Florian J, Kiss, Máté G, Enders, Lennart, Weißer, Juliane, Göderle, Laura, Lambert, Jordi, Frommlet, Florian, Mueller, André, Hendrikx, Tim, Ozsvar-Kozma, Maria, Porsch, Florentina, Willen, Laure, Afonyushkin, Taras, Murphy, Jane E, Fogelstrand, Per, Donzé, Olivier, Pasterkamp, Gerard, Hoke, Matthias, Kubicek, Stefan, Jørgensen, Helle F, Danchin, Nicolas, Simon, Tabassome, Scharnagl, Hubert, März, Winfried, Borén, Jan, Hess, Henry, Mallat, Ziad, Schneider, Pascal, and Binder, Christoph J

Published
2021

136. Oxidation-Specific Epitopes in Non-Alcoholic Fatty Liver Disease

Author

Hendrikx, Tim and Binder, Christoph J.

Subjects
Epitopes, Oxidative Stress, Endocrinology, Endocrinology, Diabetes and Metabolism, oxidation-specific epitopes, Animals, Humans, non-alcoholic fatty liver disease, lipid peroxidation, Review, innate immunity, steatohepatitis (NASH), Oxidation-Reduction
Abstract

An improper balance between the production and elimination of intracellular reactive oxygen species causes increased oxidative stress. Consequently, DNA, RNA, proteins, and lipids are irreversibly damaged, leading to molecular modifications that disrupt normal function. In particular, the peroxidation of lipids in membranes or lipoproteins alters lipid function and promotes formation of neo-epitopes, such as oxidation-specific epitopes (OSEs), which are found to be present on (lipo)proteins, dying cells, and extracellular vesicles. Accumulation of OSEs and recognition of OSEs by designated pattern recognition receptors on immune cells or soluble effectors can contribute to the development of chronic inflammatory diseases. In line, recent studies highlight the involvement of modified lipids and OSEs in different stages of the spectrum of non-alcoholic fatty liver disease (NAFLD), including inflammatory non-alcoholic steatohepatitis (NASH), fibrosis, and hepatocellular carcinoma. Targeting lipid peroxidation products shows high potential in the search for novel, better therapeutic strategies for NASH.

Published
2020

138. Complement factor H binds malondialdehyde epitopes and protects from oxidative stress

Author

Weismann, David, Hartvigsen, Karsten, Lauer, Nadine, Bennett, Keiryn L., Scholl, Hendrik P.N., Issa, Peter Charbel, Cano, Marisol, Brandstatter, Hubert, Tsimikas, Sotirios, Skerka, Christine, Superti-Furga, Giulio, Handa, James T., Zipfel, Peter F., Witztum, Joseph L., and Binder, Christoph J.

Subjects
Complement factor H -- Health aspects -- Research, Macular degeneration -- Risk factors -- Care and treatment -- Research, Oxidative stress -- Physiological aspects -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Oxidative stress and enhanced lipid peroxidation are linked to many chronic inflammatory diseases, including age-related macular degeneration (AMD). AMD is the leading cause of blindness in Western societies, but its aetiology remains largely unknown. Malondialdehyde (MDA) is a common lipid peroxidation product that accumulates in many pathophysiological processes, including AMD. Here we identify complement factor H (CFH) as a major MDA-binding protein that can block both the uptake of MDA-modified proteins by macrophages and MDA-induced proinflammatory effects in vivo in mice. The CFH polymorphism H402, which is strongly associated with AMD, markedly reduces the ability of CFH to bind MDA, indicating a causal link to disease aetiology. Our findings provide important mechanistic insights into innate immune responses to oxidative stress, which may be exploited in the prevention of and therapy for AMD and other chronic inflammatory diseases., Increased oxidative stress has been implicated in the pathogenesis of many different diseases (1). As a consequence of oxidative stress, proteins, lipids and DNA can be damaged, often resulting in [...]

Published
2011
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139. CCL17-expressing dendritic cells drive atherosclerosis by restraining regulatory T cell homeostasis in mice

Author

Weber, Christian, Meiler, Svenja, Doring, Yvonne, Koch, Miriam, Drechsler, Maik, Megens, Remco T.A., Rowinska, Zuzanna, Bidzhekov, Kiril, Fecher, Caroline, Ribechini, Eliana, van Zandvoort, Marc A.M.J., Binder, Christoph J., Jelinek, Ivett, Hristov, Mihail, Boon, Louis, Jung, Steffen, Korn, Thomas, Lutz, Manfred B., Forster, Irmgard, Zenke, Martin, Hieronymus, Thomas, Junt, Tobias, and Zernecke, Alma

Subjects
T cells -- Physiological aspects -- Research, Dendritic cells -- Physiological aspects -- Research, Atherosclerosis -- Risk factors -- Research -- Development and progression, Chemokines -- Physiological aspects -- Research, Health care industry
Abstract

Immune mechanisms are known to control the pathogenesis of atherosclerosis. However, the exact role of DCs, which are essential for priming of immune responses, remains elusive. We have shown here [...]

Published
2011
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141. Increasing test specificity without impairing sensitivity: lessons learned from SARS-CoV-2 serology

Author

Perkmann, Thomas, Koller, Thomas, Perkmann-Nagele, Nicole, Ozsvar-Kozma, Maria, Eyre, David, Matthews, Philippa, Bown, Abbie, Stoesser, Nicole, Breyer, Marie-Kathrin, Breyer-Kohansal, Robab, Burghuber, Otto C, Hartl, Slyvia, Aletaha, Daniel, Sieghart, Daniela, Quehenberger, Peter, Marculescu, Rodrig, Mucher, Patrick, Radakovics, Astrid, Klausberger, Miriam, Duerkop, Mark, Holzer, Barba, Hartmann, Boris, Strassl, Robert, Leitner, Gerda, Grebien, Florian, Gerner, Wilhelm, Grabherr, Reingard, Wagner, Oswald F, Binder, Christoph J, and Haslacher, Helmuth

Abstract

BackgroundSerological tests are widely used in various medical disciplines for diagnostic and monitoring purposes. Unfortunately, the sensitivity and specificity of test systems are often poor, leaving room for false-positive and false-negative results. However, conventional methods were used to increase specificity and decrease sensitivity and vice versa. Using SARS-CoV-2 serology as an example, we propose here a novel testing strategy: the ‘sensitivity improved two-test’ or ‘SIT²’ algorithm.MethodsSIT² involves confirmatory retesting of samples with results falling in a predefined retesting zone of an initial screening test, with adjusted cut-offs to increase sensitivity. We verified and compared the performance of SIT² to single tests and orthogonal testing (OTA) in an Austrian cohort (1117 negative, 64 post-COVID-positive samples) and validated the algorithm in an independent British cohort (976 negatives and 536 positives).ResultsThe specificity of SIT² was superior to single tests and non-inferior to OTA. The sensitivity was maintained or even improved using SIT² when compared with single tests or OTA. SIT² allowed correct identification of infected individuals even when a live virus neutralisation assay could not detect antibodies. Compared with single testing or OTA, SIT² significantly reduced total test errors to 0.46% (0.24–0.65) or 1.60% (0.94–2.38) at both 5% or 20% seroprevalence.ConclusionFor SARS-CoV-2 serology, SIT² proved to be the best diagnostic choice at both 5% and 20% seroprevalence in all tested scenarios. It is an easy to apply algorithm and can potentially be helpful for the serology of other infectious diseases.

Published
2023
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142. Oxidation-specific epitopes are dominant targets of innate natural antibodies in mice and humans

Author

Chou, Meng-Yun, Fogelstrand, Linda, Hartvigsen, Karsten, Hansen, Lotte F., Woelkers, Douglas, Shaw, Peter X., Choi, Jeomil, Perkmann, Thomas, Backhed, Fredrik, Miller, Yury I., Horkko, Sohvi, Corr, Maripat, Witztum, Joseph L., and Binder, Christoph J.

Subjects
Atherosclerosis -- Risk factors, Atherosclerosis -- Genetic aspects, Atherosclerosis -- Care and treatment, Atherosclerosis -- Research, Hypercholesterolemia -- Risk factors, Hypercholesterolemia -- Care and treatment, Hypercholesterolemia -- Research, Blood lipoproteins -- Physiological aspects, Blood lipoproteins -- Genetic aspects, Blood lipoproteins -- Research, Lipoproteins -- Physiological aspects, Lipoproteins -- Genetic aspects, Lipoproteins -- Research, Proteolipids -- Physiological aspects, Proteolipids -- Genetic aspects, Proteolipids -- Research, Oxidative stress -- Physiological aspects, Oxidative stress -- Research
Abstract

Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of oxidized lipoproteins and apoptotic cells. Adaptive immune responses to various oxidation-specific epitopes play an important role in atherogenesis. However, accumulating evidence suggests that these epitopes are also recognized by innate receptors, such as scavenger receptors on macrophages, and plasma proteins, such as C-reactive protein (CRP). Here, we provide multiple lines of evidence that oxidation-specific epitopes constitute a dominant, previously unrecognized target of natural Abs (NAbs) in both mice and humans. Using reconstituted mice expressing solely IgM NAbs, we have shown that approximately 30% of all NAbs bound to model oxidation-specific epitopes, as well as to atherosclerotic lesions and apoptotic cells. Because oxidative processes are ubiquitous, we hypothesized that these epitopes exert selective pressure to expand NAbs, which in turn play an important role in mediating homeostatic functions consequent to inflammation and cell death, as demonstrated by their ability to facilitate apoptotic cell clearance. These findings provide novel insights into the functions of NAbs in mediating host homeostasis and into their roles in health and diseases, such as chronic inflammatory diseases and atherosclerosis., Introduction Although hypercholesterolemia is necessary for the initiation and progression of atherosclerosis, there is now abundant evidence that immune mechanisms are also central to all phases of lesion development (1), [...]

Published
2009

143. Hematopoietic expression of a chimeric murine‐human CALR oncoprotein allows the assessment of anti‐CALR antibody immunotherapies in vivo

Author

Achyutuni, Sarada, primary, Nivarthi, Harini, additional, Majoros, Andrea, additional, Hug, Eva, additional, Schueller, Christina, additional, Jia, Ruochen, additional, Varga, Cecilia, additional, Schuster, Michael, additional, Senekowitsch, Martin, additional, Tsiantoulas, Dimitris, additional, Kavirayani, Anoop, additional, Binder, Christoph J, additional, Bock, Christoph, additional, Zagrijtschuk, Oleh, additional, and Kralovics, Robert, additional

Published
2021
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144. A comprehensive antigen production and characterisation study for easy-to-implement, specific and quantitative SARS-CoV-2 serotests

Author

Klausberger, Miriam, primary, Duerkop, Mark, additional, Haslacher, Helmuth, additional, Wozniak-Knopp, Gordana, additional, Cserjan-Puschmann, Monika, additional, Perkmann, Thomas, additional, Lingg, Nico, additional, Aguilar, Patricia Pereira, additional, Laurent, Elisabeth, additional, De Vos, Jelle, additional, Hofner, Manuela, additional, Holzer, Barbara, additional, Stadler, Maria, additional, Manhart, Gabriele, additional, Vierlinger, Klemens, additional, Egger, Margot, additional, Milchram, Lisa, additional, Gludovacz, Elisabeth, additional, Marx, Nicolas, additional, Köppl, Christoph, additional, Tauer, Christopher, additional, Beck, Jürgen, additional, Maresch, Daniel, additional, Grünwald-Gruber, Clemens, additional, Strobl, Florian, additional, Satzer, Peter, additional, Stadlmayr, Gerhard, additional, Vavra, Ulrike, additional, Huber, Jasmin, additional, Wahrmann, Markus, additional, Eskandary, Farsad, additional, Breyer, Marie-Kathrin, additional, Sieghart, Daniela, additional, Quehenberger, Peter, additional, Leitner, Gerda, additional, Strassl, Robert, additional, Egger, Alexander E., additional, Irsara, Christian, additional, Griesmacher, Andrea, additional, Hoermann, Gregor, additional, Weiss, Günter, additional, Bellmann-Weiler, Rosa, additional, Loeffler-Ragg, Judith, additional, Borth, Nicole, additional, Strasser, Richard, additional, Jungbauer, Alois, additional, Hahn, Rainer, additional, Mairhofer, Jürgen, additional, Hartmann, Boris, additional, Binder, Nikolaus B., additional, Striedner, Gerald, additional, Mach, Lukas, additional, Weinhäusel, Andreas, additional, Dieplinger, Benjamin, additional, Grebien, Florian, additional, Gerner, Wilhelm, additional, Binder, Christoph J., additional, and Grabherr, Reingard, additional

Published
2021
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145. Pharmacologic modulation of intracellular Na+ concentration with ranolazine impacts inflammatory response in humans and mice.

Author

Lenz, Max, Salzmann, Manuel, Ciotu, Cosmin I., Kaun, Christoph, Krychtiuk, Konstantin A., Likozar, Andreja Rehberger, Sebestjen, Miran, Goederle, Laura, Rauscher, Sabine, Krivaja, Zoriza, Binder, Christoph J., Huber, Kurt, Hengstenberg, Christian, Podesser, Bruno K., Fischer, Michael J. M., Wojta, Johann, Hohensinner, Philipp J., and Speidl, Walter S.

Subjects
INFLAMMATION, ACUTE coronary syndrome, CORONARY artery disease, ATHEROSCLEROTIC plaque, HIGH-fat diet
Abstract

Changes in Ca2+ influx during proinflammatory stimulation modulates cellular responses, including the subsequent activation of inflammation. Whereas the involvement of Ca2+ has been widely acknowledged, little is known about the role of Na+. Ranolazine, a piperazine derivative and established antianginal drug, is known to reduce intracellular Na+ as well as Ca2+ levels. In stable coronary artery disease patients (n = 51) we observed reduced levels of high-sensitive C-reactive protein (CRP) 3 mo after the start of ranolazine treatment (n = 25) as compared to the control group. Furthermore, we found that in 3,808 acute coronary syndrome patients of the MERLINTIMI 36 trial, individuals treated with ranolazine (1,934 patients) showed reduced CRP values compared to placebo-treated patients. The antiinflammatory effects of sodium modulation were further confirmed in an atherosclerotic mouse model. LDL-/- mice on a high-fat diet were treated with ranolazine, resulting in a reduced atherosclerotic plaque burden, increased plaque stability, and reduced activation of the immune system. Pharmacological Na+ inhibition by ranolazine led to reduced express of adhesion molecules and proinflammatory cytokines and reduced adhesion of leukocytes to activated endothelium both in vitro and in vivo. We demonstrate that functional Na+ shuttling is required for a full cellular response to inflammation and that inhibition of Na+ influx results in an attenuated inflammatory reaction. In conclusion, we demonstrate that inhibition of Na+-Ca2+ exchange during inflammation reduces the inflammatory response in human endothelial cells in vitro, in a mouse atherosclerotic disease model, and in human patients. [ABSTRACT FROM AUTHOR]

Published
2022
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147. Clinical validation of the Siemens quantitative SARS-CoV-2 spike IgG assay (sCOVG) reveals improved sensitivity and a good correlation with virus neutralization titers

Author

Irsara, Christian, primary, Egger, Alexander E., additional, Prokop, Wolfgang, additional, Nairz, Manfred, additional, Loacker, Lorin, additional, Sahanic, Sabina, additional, Pizzini, Alex, additional, Sonnweber, Thomas, additional, Holzer, Barbara, additional, Mayer, Wolfgang, additional, Schennach, Harald, additional, Loeffler-Ragg, Judith, additional, Bellmann-Weiler, Rosa, additional, Hartmann, Boris, additional, Tancevski, Ivan, additional, Weiss, Günter, additional, Binder, Christoph J., additional, Anliker, Markus, additional, Griesmacher, Andrea, additional, and Hoermann, Gregor, additional

Published
2021
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148. Rituximab in patients with acute ST-elevation myocardial infarction: an experimental medicine safety study

Author

Zhao, Tian X, primary, Aetesam-Ur-Rahman, Muhammad, additional, Sage, Andrew P, additional, Victor, Saji, additional, Kurian, Rincy, additional, Fielding, Sarah, additional, Ait-Oufella, Hafid, additional, Chiu, Yi-Da, additional, Binder, Christoph J, additional, Mckie, Mikel, additional, Hoole, Stephen P, additional, and Mallat, Ziad, additional

Published
2021
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150. Low-density lipoproteins cause atherosclerotic cardiovascular disease:\ud pathophysiological, genetic and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel

Author

Boren, Jan, Chapman, M. John, Krauss, Ronald M., Packard, Chris J., Bentzon, Jacob, Binder, Christoph J., Daeman, Mat J., Demer, Linda L., Hegele, Robert A., Nicholls, Stephen J., Nordestgaard, Borge G., Watts, Gerald F., Bruckert, Eric, Fazio, Sergio, Ference, Brian A., Graham, Ian, Horton, Jay D., Landmesser, Ulf, Laufs, Ulrich, Masana, Luis, Pasterkamp, Gerard, Raal, Frederick J., Ray, Kausik K., Schunkert, Heribert, Taskinen, Marja-Ritta, van de Sluis, Bart, Wiklund, Olov, Tokogozoglu, Lale, Catapano, Alberico L., and Ginsberg, Henry N.

Subjects
ComputingMethodologies_COMPUTERGRAPHICS
Abstract

Graphic abstract available.

Published
2020

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