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1. DNMT3A clonal hematopoiesis-driver mutations induce cardiac fibrosis by paracrine activation of fibroblasts

Author

Shumliakivska, Mariana, Luxán, Guillermo, Hemmerling, Inga, Scheller, Marina, Li, Xue, Müller-Tidow, Carsten, Schuhmacher, Bianca, Sun, Zhengwu, Dendorfer, Andreas, Debes, Alisa, Glaser, Simone-Franziska, Muhly-Reinholz, Marion, Kirschbaum, Klara, Hoffmann, Jedrzej, Nagel, Eike, Puntmann, Valentina O., Cremer, Sebastian, Leuschner, Florian, Abplanalp, Wesley Tyler, John, David, Zeiher, Andreas M., and Dimmeler, Stefanie

Published
2024
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2. The histone demethylase JMJD2B regulates endothelial-to-mesenchymal transition

Author

Glaser, Simone F., Heumüller, Andreas W., Tombor, Lukas, Hofmann, Patrick, Muhly-Reinholz, Marion, Fischer, Ariane, Gunther, Stefan, Kokot, Karoline E., Hassel, David, Kumar, Sandeep, Jo, Hanjoong, Boon, Reinier A., Abplanalp, Wesley, John, David, Boeckel, Jes-Niels, and Dimmeler, Stefanie

Published
2020

4. Single cell sequencing reveals endothelial plasticity with transient mesenchymal activation after myocardial infarction

Author

Tombor, Lukas S., John, David, Glaser, Simone F., Luxán, Guillermo, Forte, Elvira, Furtado, Milena, Rosenthal, Nadia, Baumgarten, Nina, Schulz, Marcel H., Wittig, Janina, Rogg, Eva-Maria, Manavski, Yosif, Fischer, Ariane, Muhly-Reinholz, Marion, Klee, Kathrin, Looso, Mario, Selignow, Carmen, Acker, Till, Bibli, Sofia-Iris, Fleming, Ingrid, Patrick, Ralph, Harvey, Richard P., Abplanalp, Wesley T., and Dimmeler, Stefanie

Published
2021
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6. Abstract P3070: Aortic Valve Calcification Is Accelerated By DNMT3A And TET2 Gene Driver Mutations Associated With Clonal Hematopoiesis

Author

Abplanalp, Wesley T, primary, Schuhmacher, Bianca, additional, Mas-Peiro, Silvia, additional, Zuriaga, Maria A, additional, Matesanz, Nuria, additional, Fuster, Jose J, additional, John, David, additional, Muhly-Reinholz, Marion, additional, Vasa-Nicotera, Mariuca, additional, Merten, Maximilian, additional, Dimmeler, Stefanie, additional, and Zeiher, Andreas M, additional

Published
2023
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7. Hematopoietic Deficiency of the Long Noncoding RNA MALAT1 Promotes Atherosclerosis and Plaque Inflammation

Author

Cremer, Sebastian, Michalik, Katharina M., Fischer, Ariane, Pfisterer, Larissa, Jaé, Nicolas, Winter, Carla, Boon, Reinier A., Muhly-Reinholz, Marion, John, David, Uchida, Shizuka, Weber, Christian, Poller, Wolfgang, Günther, Stefan, Braun, Thomas, Li, Daniel Y., Maegdefessel, Lars, Perisic Matic, Ljubica, Hedin, Ulf, Soehnlein, Oliver, Zeiher, Andreas, and Dimmeler, Stefanie

Published
2019
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10. Locus-conserved circular RNA cZNF292 controls endothelial cell flow responses

Author

Heumüller, Andreas W., Jones, Alisha N., Mourão, André, Klangwart, Marius, Shi, Chenyue, Wittig, Ilka, Fischer, Ariane, Muhly-Reinholz, Marion, Buchmann, Giulia K., Dieterich, Christoph, Potente, Michael, Braun, Thomas, Grote, Phillip, Jaé, Nicolas, Sattler, Michael, and Dimmeler, Stefanie

Subjects
Intracellular Signaling Peptides and Proteins, Endothelial Cells, RNA, Circular, DNA-Binding Proteins, Mice, Inbred C57BL, Mice, Cardiovascular and Metabolic Diseases, Blood Circulation, Animals, Humans, Syndecan-4, Endothelium, Vascular, Cytoskeleton, Rna, Circular, Non-coding, Protein Binding, Transcription Factors
Abstract

Background: Circular RNAs (circRNAs) are generated by back-splicing of mostly mRNAs and are gaining increasing attention as a novel class of regulatory RNAs that control various cellular functions. However, their physiological roles and functional conservation in vivo are rarely addressed, given the inherent challenges of their genetic inactivation. Here we aimed to identify locus conserved circRNAs in mice and humans, which can be genetically deleted due to retained intronic elements not contained in the mRNA host gene to eventually address functional conservation. Methods: Mechanistically, we identified the protein syndesmos (SDOS) to specifically interact with cZNF292 in endothelial cells by RNA affinity purification and subsequent mass spectrometry analysis. Silencing of SDOS or its protein binding partner Syndecan-4, or mutation of the SDOS-cZNF292 binding site, prevented laminar flow-induced cytoskeletal reorganisation thereby recapitulating cZfp292 phenotypes. Results: Combining published endothelial RNA sequencing datasets with circRNAs of the circATLAS databank, we identified locus-conserved circRNA retaining intronic elements between mice and humans. CRISPR/Cas9 mediated genetic depletion of the top expressed circRNA cZfp292 resulted in an altered endothelial morphology and aberrant flow alignment in the aorta in vivo. Consistently, depletion of cZNF292 in endothelial cells in vitro abolished laminar flow-induced alterations in cell orientation, paxillin localisation and focal adhesion organisation. Conclusion: Together, our data reveal a hitherto unknown role of cZNF292/cZfp292 in endothelial flow responses, which influences endothelial shape.

Published
2022

11. Locus-Conserved Circular RNA cZNF292 Controls Endothelial Cell Flow Responses

Author

Heumüller, Andreas W., primary, Jones, Alisha N., additional, Mourão, André, additional, Klangwart, Marius, additional, Shi, Chenyue, additional, Wittig, Ilka, additional, Fischer, Ariane, additional, Muhly-Reinholz, Marion, additional, Buchmann, Giulia K., additional, Dieterich, Christoph, additional, Potente, Michael, additional, Braun, Thomas, additional, Grote, Phillip, additional, Jaé, Nicolas, additional, Sattler, Michael, additional, and Dimmeler, Stefanie, additional

Published
2022
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12. Single cell sequencing reveals endothelial plasticity with transient mesenchymal activation after myocardial infarction

Author

Tombor, Lukas, John, David, Glaser, Simone F., Luxán, Guillermo, Forte, Elvira, Furtado, Milena, Rosenthal, Nadia, Baumgarten, Nina, Schulz, Marcel Holger, Wittig, Janina, Rogg, Eva-Maria, Manavski, Yosif, Fischer, Ariane, Muhly-Reinholz, Marion, Klee, Kathrin, Looso, Mario, Selignow, Carmen, Acker, Till, Bibli, Sofia Iris, Fleming, Ingrid, Patrick, Ralph, Harvey, Richard P., Abplanalp, Wesley T., Dimmeler, Stefanie, Tombor, Lukas, John, David, Glaser, Simone F., Luxán, Guillermo, Forte, Elvira, Furtado, Milena, Rosenthal, Nadia, Baumgarten, Nina, Schulz, Marcel Holger, Wittig, Janina, Rogg, Eva-Maria, Manavski, Yosif, Fischer, Ariane, Muhly-Reinholz, Marion, Klee, Kathrin, Looso, Mario, Selignow, Carmen, Acker, Till, Bibli, Sofia Iris, Fleming, Ingrid, Patrick, Ralph, Harvey, Richard P., Abplanalp, Wesley T., and Dimmeler, Stefanie

Abstract

Endothelial cells play a critical role in the adaptation of tissues to injury. Tissue ischemia induced by infarction leads to profound changes in endothelial cell functions and can induce transition to a mesenchymal state. Here we explore the kinetics and individual cellular responses of endothelial cells after myocardial infarction by using single cell RNA sequencing. This study demonstrates a time dependent switch in endothelial cell proliferation and inflammation associated with transient changes in metabolic gene signatures. Trajectory analysis reveals that the majority of endothelial cells 3 to 7 days after myocardial infarction acquire a transient state, characterized by mesenchymal gene expression, which returns to baseline 14 days after injury. Lineage tracing, using the Cdh5-CreERT2;mT/mG mice followed by single cell RNA sequencing, confirms the transient mesenchymal transition and reveals additional hypoxic and inflammatory signatures of endothelial cells during early and late states after injury. These data suggest that endothelial cells undergo a transient mes-enchymal activation concomitant with a metabolic adaptation within the first days after myocardial infarction but do not acquire a long-term mesenchymal fate. This mesenchymal activation may facilitate endothelial cell migration and clonal expansion to regenerate the vascular network.

Published
2021

13. Erratum:The histone demethylase JMJD2B regulates endothelial-to-mesenchymal transition (Proceedings of the National Academy of Sciences of the United States of America (2020) 117 (4180-4187) DOI: 10.1073/pnas.1913481117)

Author

Glaser, Simone F., Heumüller, Andreas W., Tombor, Lukas, Hofmann, Patrick, Muhly-Reinholz, Marion, Fischer, Ariane, Günther, Stefan, Kokot, Karoline E., Okada, Hitoshi, Hassel, David, Kumar, Sandeep, Jo, Hanjoong, Boon, Reinier A., Abplanalp, Wesley, John, David, Boeckel, Jes Niels, and Dimmeler, Stefanie

Abstract

Correction for “The histone demethylase JMJD2B regulates endothelial-to-mesenchymal transition,” by Simone F. Glaser, Andreas W. Heumüller, Lukas Tombor, Patrick Hofmann, Marion Muhly-Reinholz, Ariane Fischer, Stefan Günther, Karoline E. Kokot, David Hassel, Sandeep Kumar, Hanjoong Jo, Reinier A. Boon, Wesley Abplanalp, David John, Jes-Niels Boeckel, and Stefanie Dimmeler, which was first published February 7, 2020; 10.1073/pnas.1913481117 (Proc. Natl. Acad. Sci. U.S.A. 117, 4180-4187). The authors note that Hitoshi Okada should be added to the author list between Karoline E. Kokot and David Hassel. Hitoshi Okada should be credited with providing mice. The corrected author line, affiliation line, and author contributions appear below. The online version has been corrected.

Published
2020

14. Transcriptional heterogeneity of fibroblasts is a hallmark of the aging heart

Author

Vidal, Ramon, primary, Wagner, Julian Uwe Gabriel, additional, Braeuning, Caroline, additional, Fischer, Cornelius, additional, Patrick, Ralph, additional, Tombor, Lukas, additional, Muhly-Reinholz, Marion, additional, John, David, additional, Kliem, Magdalena, additional, Conrad, Thomas, additional, Guimarães-Camboa, Nuno, additional, Harvey, Richard, additional, Dimmeler, Stefanie, additional, and Sauer, Sascha, additional

Published
2019
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15. Switch in Laminin β2 to Laminin β1 Isoforms During Aging Controls Endothelial Cell Functions—Brief Report

Author

Wagner, Julian U.G., primary, Chavakis, Emmanouil, additional, Rogg, Eva-Maria, additional, Muhly-Reinholz, Marion, additional, Glaser, Simone F., additional, Günther, Stefan, additional, John, David, additional, Bonini, Francesca, additional, Zeiher, Andreas M., additional, Schaefer, Liliana, additional, Hannocks, Melanie-Jane, additional, Boon, Reinier A., additional, and Dimmeler, Stefanie, additional

Published
2018
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16. Comparison of MOLLI, shMOLLLI, and SASHA in discrimination between health and disease and relationship with histologically derived collagen volume fraction

Author

Child, Nicholas, primary, Suna, Gonca, additional, Dabir, Darius, additional, Yap, May-Lin, additional, Rogers, Toby, additional, Kathirgamanathan, Misha, additional, Arroyo-Ucar, Eduardo, additional, Hinojar, Rocio, additional, Mahmoud, Islam, additional, Young, Christopher, additional, Wendler, Olaf, additional, Mayr, Manuel, additional, Sandhu, Banher, additional, Morton, Geraint, additional, Muhly-Reinholz, Marion, additional, Dimmeler, Stefanie, additional, Nagel, Eike, additional, and Puntmann, Valentina O, additional

Published
2017
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17. Comparison of MOLLI, shMOLLLI, and SASHA in discrimination between health and disease and relationship with histologically derived collagen volume fraction.

Author

Child, Nicholas, Suna, Gonca, Dabir, Darius, Yap, May-lin, Rogers, Toby, Kathirgamanathan, Misha, Arroyo-Ucar, Eduardo, Hinojar, Rocio, Mahmoud, Islam, Young, Christopher, Wendler, Olaf, Mayr, Manuel, Sandhu, Banher, Morton, Geraint, Muhly-Reinholz, Marion, Dimmeler, Stefanie, Nagel, Eike, and Puntmann, Valentina O.

Subjects
AORTIC stenosis, CARDIOMYOPATHIES, DILATED cardiomyopathy, BIOPSY, C-reactive protein, CARDIOVASCULAR system physiology, COLLAGEN, MAGNETIC resonance imaging, RESEARCH evaluation, SURGICAL therapeutics, TROPONIN, DIAGNOSIS
Abstract

Aims To determine the bioequivalence of several T1 mapping sequences in myocardial characterization of diffuse myocardial fibrosis. Methods and results We performed an intra-individual sequence comparison of three types of T1 mapping sequences [MOdified Look-Locker Inversion recovery (MOLLI), Shortened MOdified Look-Locker Inversion recovery ((sh)MOLLI), and SAturation recovery single-SHot Acquisition (SASHA)]. We employed two model diseases of diffuse interstitial fibrosis [patients with non-ischaemic dilated cardiomyopathy (NIDCM), n = 32] and aortic stenosis [(AS), n = 25)]. Twenty-six healthy individuals served as controls. Relationship with collagen volume fraction (CVF) was assessed using endomyocardial biopsies (EMB) intraoperatively in 12 AS patients. T2 mapping (GraSE) was also performed. Myocardial native T1 with MOLLI and shMOLLI showed, firstly, an excellent discriminatory accuracy between health and disease [area under the curves (P-value): 0.94 (0.88-0.99); 0.87 (0.79-0.94); 0.61 (0.49--0.72)], secondly, relationship between histological CVF [native T1 MOLLI vs. shMOLLI vs. SASHA: r = 0.582 (P = 0.027), r = 0.524 (P = 0.046), r = 0.443 (P = 0.150)], and thirdly, with native T2 [r = 0.628(P < 0.001), r = 0.459 (P = 0.003), r = 0.211 (P = 0.083)]. The respective relationships for extracellular volume fraction with CVF [r = 0.489 (P = 0.044), r = 0.417 (0.071), r = 0.353 (P = 0.287)] were significant for MOLLI, but not other sequences. In AS patients, native T2 was significantly higher compared to controls, and associated with levels of C-reactive protein and troponin. Conclusion T1 mapping sequences differ in their bioequivalence for discrimination between health and disease as well as associations with diffuse myocardial fibrosis." [ABSTRACT FROM AUTHOR]

Published
2018
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20. Heparin Disrupts the CXCR4/SDF-1 Axis and Impairs the Functional Capacity of Bone Marrow–Derived Mononuclear Cells Used for Cardiovascular Repair

Author

Seeger, Florian H., primary, Rasper, Tina, additional, Fischer, Ariane, additional, Muhly-Reinholz, Marion, additional, Hergenreider, Eduard, additional, Leistner, David M., additional, Sommer, Katharina, additional, Manavski, Yosif, additional, Henschler, Reinhard, additional, Chavakis, Emmanouil, additional, Assmus, Birgit, additional, Zeiher, Andreas M., additional, and Dimmeler, Stefanie, additional

Published
2012
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21. Sustained Persistence of Transplanted Proangiogenic Cells Contributes to Neovascularization and Cardiac Function After Ischemia

Author

Ziebart, Thomas, primary, Yoon, Chang-Hwan, additional, Trepels, Thomas, additional, Wietelmann, Astrid, additional, Braun, Thomas, additional, Kiessling, Fabian, additional, Stein, Stefan, additional, Grez, Manuel, additional, Ihling, Christian, additional, Muhly-Reinholz, Marion, additional, Carmona, Guillaume, additional, Urbich, Carmen, additional, Zeiher, Andreas M., additional, and Dimmeler, Stefanie, additional

Published
2008
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22. ω-3 Fatty acids suppress monocyte adhesion to human endothelial cells: role of endothelial PAF generation

Author

Mayer, Konstantin, primary, Merfels, Martina, additional, Muhly-Reinholz, Marion, additional, Gokorsch, Stephanie, additional, Rosseau, Simone, additional, Lohmeyer, Jürgen, additional, Schwarzer, Nicole, additional, Krüll, Matthias, additional, Suttorp, Norbert, additional, Grimminger, Friedrich, additional, and Seeger, Werner, additional

Published
2002
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24. &omega-3 Fatty acids suppress monocyte adhesion to human endothelial cells: role of endothelial PAF generation.

Author

Mayer, Konstantin, Merfels, Martina, Muhly-Reinholz, Marion, Gokorsch, Stephanie, Rosseau, Simone, Lohmeyer, Jurgen, Schwarzer, Nicole, Krull, Matthias, Suttorp, Norbert, Grimminger, Friedrich, and Seeger, Werner

Subjects
CELL communication, EICOSAPENTAENOIC acid, ARACHIDONIC acid
Abstract

Provides information on a study that investigated the impact of arachidonic acid versus eicosapentaenoic acid on monocyte-endothelial interaction under laminar flow conditions in human endothelial cells undergoing cytokine stimulation in vitro. Methodology of the study; Results and discussion on the study.

Published
2002
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25. In vitro mimicry of essential fatty acid deficiency in human endothelial cells by TNFalpha impact of omega-3 versus omega-6 fatty acids.

Author

Mayer, Konstantin, Schmidt, Reinhold, Muhly-Reinholz, Marion, Bögeholz, Tina, Gokorsch, Stephanie, Grimminger, Friedrich, and Seeger, Werner

Abstract

Severe endothelial abnormalities are a prominent feature in sepsis with cytokines such as tumor necrosis factor (TNF)alpha being implicated in the pathogenesis. As mimic to inflammation, human umbilical vascular endothelial cells (HUVEC) were incubated with TNFalpha for 22 h, in the absence or presence of the omega-6 fatty acid (FA), arachidonic acid (AA), or the alternative omega-3 FA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). TNFalpha caused marked alterations in the PUFA profile and long chain PUFA content of total phospholipids (PL) decreased. In contrast, there was a compensatory increase in mead acid [MA, 20:3(omega-9)], the hallmark acid of the essential fatty acid deficiency (EFAD) syndrome. Corresponding changes were noted in phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol, but not in the sphingomyelin fraction. Supplementation with AA, EPA, or DHA markedly increased the respective FA contents in the PL pools, suppressed the increase in MA, and resulted in a shift either toward further predominance of omega-6 or predominance of omega-3 FA. We conclude that short-term TNFalpha incubation of HUVEC causes an EFAD state hitherto only described for long-term malnutrition, and that endothelial cells are susceptible to differential influence by omega-3 versus omega-6 FA supplementation under these conditions.

Published
2002

26. Comparison of MOLLI, shMOLLLI, and SASHA in discrimination between health and disease and relationship with histologically derived collagen volume fraction.

Author

Child N, Suna G, Dabir D, Yap ML, Rogers T, Kathirgamanathan M, Arroyo-Ucar E, Hinojar R, Mahmoud I, Young C, Wendler O, Mayr M, Sandhu B, Morton G, Muhly-Reinholz M, Dimmeler S, Nagel E, and Puntmann VO

Subjects
Adult, Aged, Cardiomyopathies pathology, Cohort Studies, Contrast Media, Female, Heart Failure pathology, Humans, Male, Middle Aged, Phantoms, Imaging, Predictive Value of Tests, Reproducibility of Results, Retrospective Studies, Sensitivity and Specificity, Body Surface Potential Mapping methods, Cardiomyopathies diagnostic imaging, Heart Failure diagnostic imaging, Image Interpretation, Computer-Assisted methods, Magnetic Resonance Imaging, Cine methods
Abstract

Aims: To determine the bioequivalence of several T1 mapping sequences in myocardial characterization of diffuse myocardial fibrosis., Methods and Results: We performed an intra-individual sequence comparison of three types of T1 mapping sequences [MOdified Look-Locker Inversion recovery (MOLLI), Shortened MOdified Look-Locker Inversion recovery ((sh)MOLLI), and SAturation recovery single-SHot Acquisition (SASHA)]. We employed two model diseases of diffuse interstitial fibrosis [patients with non-ischaemic dilated cardiomyopathy (NIDCM), n = 32] and aortic stenosis [(AS), n = 25)]. Twenty-six healthy individuals served as controls. Relationship with collagen volume fraction (CVF) was assessed using endomyocardial biopsies (EMB) intraoperatively in 12 AS patients. T2 mapping (GraSE) was also performed. Myocardial native T1 with MOLLI and shMOLLI showed, firstly, an excellent discriminatory accuracy between health and disease [area under the curves (P-value): 0.94 (0.88-0.99); 0.87 (0.79-0.94); 0.61 (0.49-0.72)], secondly, relationship between histological CVF [native T1 MOLLI vs. shMOLLI vs. SASHA: r = 0.582 (P = 0.027), r = 0.524 (P = 0.046), r = 0.443 (P = 0.150)], and thirdly, with native T2 [r = 0.628(P < 0.001), r = 0.459 (P = 0.003), r = 0.211 (P = 0.083)]. The respective relationships for extracellular volume fraction with CVF [r = 0.489 (P = 0.044), r = 0.417 (0.071), r = 0.353 (P = 0.287)] were significant for MOLLI, but not other sequences. In AS patients, native T2 was significantly higher compared to controls, and associated with levels of C-reactive protein and troponin., Conclusion: T1 mapping sequences differ in their bioequivalence for discrimination between health and disease as well as associations with diffuse myocardial fibrosis.

Published
2018
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