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6 results on '"von Scheidt, Moritz"'

1. Elucidation of the genetic causes of bicuspid aortic valve disease

Author

Gehlen, Jan, Stundl, Anja, Debiec, Radoslaw, Fontana, Federica, Krane, Markus, Sharipova, Dinara, Nelson, Christopher P., Al-Kassou, Baravan, Giel, Ann Sophie, Sinning, Jan Malte, Bruenger, Christopher M. H., Zelck, Carolin F., Koebbe, Laura L., Braund, Peter S., Webb, Thomas R., Hetherington, Simon, Ensminger, Stephan, Fujita, Buntaro, Mohamed, Salah A., Shrestha, Malakh, Krueger, Heike, Siepe, Matthias, Kari, Fabian Alexander, Nordbeck, Peter, Buravezky, Larissa, Kelm, Malte, Veulemans, Verena, Adam, Matti, Baldus, Stephan, Laugwitz, Karl Ludwig, Haas, Yannick, Karck, Matthias, Mehlhorn, Uwe, Conzelmann, Lars Oliver, Breitenbach, Ingo, Lebherz, Corinna, Urbanski, Paul, Kim, Won Keun, Kandels, Joscha, Ellinghaus, David, Nowak-Goettl, Ulrike, Hoffmann, Per, Wirth, Felix, Doppler, Stefanie, Lahm, Harald, Dressen, Martina, von Scheidt, Moritz, Knoll, Katharina, Kessler, Thorsten, Hengstenberg, Christian, Schunkert, Heribert, Nickenig, Georg, Noethen, Markus M., Bolger, Aidan P., Abdelilah-Seyfried, Salim, Samani, Nilesh J., Erdmann, Jeanette, Trenkwalder, Teresa, Schumacher, Johannes, Gehlen, Jan, Stundl, Anja, Debiec, Radoslaw, Fontana, Federica, Krane, Markus, Sharipova, Dinara, Nelson, Christopher P., Al-Kassou, Baravan, Giel, Ann Sophie, Sinning, Jan Malte, Bruenger, Christopher M. H., Zelck, Carolin F., Koebbe, Laura L., Braund, Peter S., Webb, Thomas R., Hetherington, Simon, Ensminger, Stephan, Fujita, Buntaro, Mohamed, Salah A., Shrestha, Malakh, Krueger, Heike, Siepe, Matthias, Kari, Fabian Alexander, Nordbeck, Peter, Buravezky, Larissa, Kelm, Malte, Veulemans, Verena, Adam, Matti, Baldus, Stephan, Laugwitz, Karl Ludwig, Haas, Yannick, Karck, Matthias, Mehlhorn, Uwe, Conzelmann, Lars Oliver, Breitenbach, Ingo, Lebherz, Corinna, Urbanski, Paul, Kim, Won Keun, Kandels, Joscha, Ellinghaus, David, Nowak-Goettl, Ulrike, Hoffmann, Per, Wirth, Felix, Doppler, Stefanie, Lahm, Harald, Dressen, Martina, von Scheidt, Moritz, Knoll, Katharina, Kessler, Thorsten, Hengstenberg, Christian, Schunkert, Heribert, Nickenig, Georg, Noethen, Markus M., Bolger, Aidan P., Abdelilah-Seyfried, Salim, Samani, Nilesh J., Erdmann, Jeanette, Trenkwalder, Teresa, and Schumacher, Johannes

Abstract

Aims The present study aims to characterize the genetic risk architecture of bicuspid aortic valve (BAV) disease, the most common congenital heart defect. Methods and results We carried out a genome-wide association study (GWAS) including 2236 BAV patients and 11 604 controls. This led to the identification of a new risk locus for BAV on chromosome 3q29. The single nucleotide polymorphism rs2550262 was genome-wide significant BAV associated (P = 3.49 x 10(-08)) and was replicated in an independent case-control sample. The risk locus encodes a deleterious missense variant in MUC4 (p.Ala4821Ser), a gene that is involved in epithelial-to-mesenchymal transformation. Mechanistical studies in zebrafish revealed that loss of Muc4 led to a delay in cardiac valvular development suggesting that loss of MUC4 may also play a role in aortic valve malformation. The GWAS also confirmed previously reported BAV risk loci at PALMD (P = 3.97 x 10(-16)), GATA4 (P = 1.61 x 10(-09)), and TEX41 (P = 7.68 x 10(-04)). In addition, the genetic BAV architecture was examined beyond the single-marker level revealing that a substantial fraction of BAV heritability is polygenic and similar to 20% of the observed heritability can be explained by our GWAS data. Furthermore, we used the largest human single-cell atlas for foetal gene expression and show that the transcriptome profile in endothelial cells is a major source contributing to BAV pathology. Conclusion Our study provides a deeper understanding of the genetic risk architecture of BAV formation on the single marker and polygenic level.

Published
2023

2. Elucidation of the genetic causes of bicuspid aortic valve disease

Author

Gehlen, Jan, Stundl, Anja, Debiec, Radoslaw, Fontana, Federica, Krane, Markus, Sharipova, Dinara, Nelson, Christopher P., Al-Kassou, Baravan, Giel, Ann Sophie, Sinning, Jan Malte, Bruenger, Christopher M. H., Zelck, Carolin F., Koebbe, Laura L., Braund, Peter S., Webb, Thomas R., Hetherington, Simon, Ensminger, Stephan, Fujita, Buntaro, Mohamed, Salah A., Shrestha, Malakh, Krueger, Heike, Siepe, Matthias, Kari, Fabian Alexander, Nordbeck, Peter, Buravezky, Larissa, Kelm, Malte, Veulemans, Verena, Adam, Matti, Baldus, Stephan, Laugwitz, Karl Ludwig, Haas, Yannick, Karck, Matthias, Mehlhorn, Uwe, Conzelmann, Lars Oliver, Breitenbach, Ingo, Lebherz, Corinna, Urbanski, Paul, Kim, Won Keun, Kandels, Joscha, Ellinghaus, David, Nowak-Goettl, Ulrike, Hoffmann, Per, Wirth, Felix, Doppler, Stefanie, Lahm, Harald, Dressen, Martina, von Scheidt, Moritz, Knoll, Katharina, Kessler, Thorsten, Hengstenberg, Christian, Schunkert, Heribert, Nickenig, Georg, Noethen, Markus M., Bolger, Aidan P., Abdelilah-Seyfried, Salim, Samani, Nilesh J., Erdmann, Jeanette, Trenkwalder, Teresa, Schumacher, Johannes, Gehlen, Jan, Stundl, Anja, Debiec, Radoslaw, Fontana, Federica, Krane, Markus, Sharipova, Dinara, Nelson, Christopher P., Al-Kassou, Baravan, Giel, Ann Sophie, Sinning, Jan Malte, Bruenger, Christopher M. H., Zelck, Carolin F., Koebbe, Laura L., Braund, Peter S., Webb, Thomas R., Hetherington, Simon, Ensminger, Stephan, Fujita, Buntaro, Mohamed, Salah A., Shrestha, Malakh, Krueger, Heike, Siepe, Matthias, Kari, Fabian Alexander, Nordbeck, Peter, Buravezky, Larissa, Kelm, Malte, Veulemans, Verena, Adam, Matti, Baldus, Stephan, Laugwitz, Karl Ludwig, Haas, Yannick, Karck, Matthias, Mehlhorn, Uwe, Conzelmann, Lars Oliver, Breitenbach, Ingo, Lebherz, Corinna, Urbanski, Paul, Kim, Won Keun, Kandels, Joscha, Ellinghaus, David, Nowak-Goettl, Ulrike, Hoffmann, Per, Wirth, Felix, Doppler, Stefanie, Lahm, Harald, Dressen, Martina, von Scheidt, Moritz, Knoll, Katharina, Kessler, Thorsten, Hengstenberg, Christian, Schunkert, Heribert, Nickenig, Georg, Noethen, Markus M., Bolger, Aidan P., Abdelilah-Seyfried, Salim, Samani, Nilesh J., Erdmann, Jeanette, Trenkwalder, Teresa, and Schumacher, Johannes

Abstract

Aims The present study aims to characterize the genetic risk architecture of bicuspid aortic valve (BAV) disease, the most common congenital heart defect. Methods and results We carried out a genome-wide association study (GWAS) including 2236 BAV patients and 11 604 controls. This led to the identification of a new risk locus for BAV on chromosome 3q29. The single nucleotide polymorphism rs2550262 was genome-wide significant BAV associated (P = 3.49 x 10(-08)) and was replicated in an independent case-control sample. The risk locus encodes a deleterious missense variant in MUC4 (p.Ala4821Ser), a gene that is involved in epithelial-to-mesenchymal transformation. Mechanistical studies in zebrafish revealed that loss of Muc4 led to a delay in cardiac valvular development suggesting that loss of MUC4 may also play a role in aortic valve malformation. The GWAS also confirmed previously reported BAV risk loci at PALMD (P = 3.97 x 10(-16)), GATA4 (P = 1.61 x 10(-09)), and TEX41 (P = 7.68 x 10(-04)). In addition, the genetic BAV architecture was examined beyond the single-marker level revealing that a substantial fraction of BAV heritability is polygenic and similar to 20% of the observed heritability can be explained by our GWAS data. Furthermore, we used the largest human single-cell atlas for foetal gene expression and show that the transcriptome profile in endothelial cells is a major source contributing to BAV pathology. Conclusion Our study provides a deeper understanding of the genetic risk architecture of BAV formation on the single marker and polygenic level.

Published
2023

3. Leukocytes carrying Clonal Hematopoiesis of Indeterminate Potential (CHIP) Mutations invade Human Atherosclerotic Plaques.

Author

CDL Onderzoek Pasterkamp, Experimentele Afd. Cardiologie 1, Child Health, Circulatory Health, von Scheidt, Moritz, Bauer, Sabine, Ma, Angela, Hao, Ke, Kessler, Thorsten, Vilne, Baiba, Wang, Ying, Hodonsky, Chani J, Ghosh, Saikat K B, Mokry, Michal, Gao, Hua, Kawai, Kenji, Sakamoto, Atsushi, Kaiser, Juliane, Bongiovanni, Dario, Fleig, Julia, Oldenbuettel, Lilith, Chen, Zhifen, Moggio, Aldo, Sager, Hendrik B, Hecker, Judith S, Bassermann, Florian, Maegdefessel, Lars, Miller, Clint L, Koenig, Wolfgang, Zeiher, Andreas M, Dimmeler, Stefanie, Graw, Matthias, Braun, Christian, Ruusalepp, Arno, Leeper, Nicholas J, Kovacic, Jason C, Björkegren, Johan L M, Schunkert, Heribert, CDL Onderzoek Pasterkamp, Experimentele Afd. Cardiologie 1, Child Health, Circulatory Health, von Scheidt, Moritz, Bauer, Sabine, Ma, Angela, Hao, Ke, Kessler, Thorsten, Vilne, Baiba, Wang, Ying, Hodonsky, Chani J, Ghosh, Saikat K B, Mokry, Michal, Gao, Hua, Kawai, Kenji, Sakamoto, Atsushi, Kaiser, Juliane, Bongiovanni, Dario, Fleig, Julia, Oldenbuettel, Lilith, Chen, Zhifen, Moggio, Aldo, Sager, Hendrik B, Hecker, Judith S, Bassermann, Florian, Maegdefessel, Lars, Miller, Clint L, Koenig, Wolfgang, Zeiher, Andreas M, Dimmeler, Stefanie, Graw, Matthias, Braun, Christian, Ruusalepp, Arno, Leeper, Nicholas J, Kovacic, Jason C, Björkegren, Johan L M, and Schunkert, Heribert

Published
2023

4. Solving the Pulmonary Hypertension Paradox in Patients With Severe Tricuspid Regurgitation by Employing Artificial Intelligence

Author

Fortmeier, Vera, Lachmann, Mark, Koerber, Maria, I, Unterhuber, Matthias, von Scheidt, Moritz, Rippen, Elena, Harmsen, Gerhard, Gercek, Muhammed, Friedrichs, Kai Peter, Roder, Fabian, Rudolph, Tanja K., Yuasa, Shinsuke, Joner, Michael, Laugwitz, Karl-Ludwig, Baldus, Stephan, Pfister, Roman, Lurz, Philipp, Rudolph, Volker, Fortmeier, Vera, Lachmann, Mark, Koerber, Maria, I, Unterhuber, Matthias, von Scheidt, Moritz, Rippen, Elena, Harmsen, Gerhard, Gercek, Muhammed, Friedrichs, Kai Peter, Roder, Fabian, Rudolph, Tanja K., Yuasa, Shinsuke, Joner, Michael, Laugwitz, Karl-Ludwig, Baldus, Stephan, Pfister, Roman, Lurz, Philipp, and Rudolph, Volker

Abstract

OBJECTIVES This study aimed to improve echocardiographic assessment of pulmonary hypertension (PH) in patients presenting with severe tricuspid regurgitation (TR). BACKGROUND Echocardiographic assessment of PH in patients with severe TR carries several pitfalls for underestimation, hence concealing the true severity of PH in very sick patients in particular, and ultimately obscuring the impact of PH on survival after transcatheter tricuspid valve intervention (TTVI). METHODS All patients in this study underwent TTVI for severe TR between 2016 and 2020. To predict the mean pulmonary artery pressure (mPAP) solely based on echocardiographic parameters, we trained an extreme gradient boosting (XGB) algorithm. The derivation cohort was constituted by 116 out of 162 patients with both echocardiography and right heart catheterization data, preprocedurally obtained, from a bicentric registry. Moreover, 142 patients from an independent institution served for external validation. RESULTS Systolic pulmonary artery pressure was consistently underestimated by echocardiography in comparison to right heart catheterization (40.3 +/- 15.9 mm Hg vs 44.1 +/- 12.9 mm Hg; P = 0.0066), and the assessment was most discrepant among patients with severe defects of the tricuspid valve and impaired right ventricular systolic function. Using 9 echocardiographic parameters as input variables, an XGB algorithm could reliably predict mPAP levels (R = 0.96, P < 2.2 x 10(-16)). Moreover, patients with elevations in predicted mPAP levels >= 29.9 mm Hg showed significantly reduced 2-year survival after TTVI (58.3% [95% CI: 41.7%-81.6%] vs 78.8% [95% CI: 68.7%-90.5%]; P = 0.026). Importantly, the poor prognosis associated with elevation in predicted mPAP levels was externally confirmed (HR for 2-year mortality: 2.9 [95% CI: 1.5-5.7]; P = 0.002). CONCLUSIONS PH in patients with severe TR can be reliably assessed based on echocardiographic parameters in conjunction with an XGB algorithm, and elevations

Published
2022

5. Applications and Limitations of Mouse Models for Understanding Human Atherosclerosis.

Author

von Scheidt, Moritz, von Scheidt, Moritz, Zhao, Yuqi, Kurt, Zeyneb, Pan, Calvin, Zeng, Lingyao, Yang, Xia, Schunkert, Heribert, Lusis, Aldons J, von Scheidt, Moritz, von Scheidt, Moritz, Zhao, Yuqi, Kurt, Zeyneb, Pan, Calvin, Zeng, Lingyao, Yang, Xia, Schunkert, Heribert, and Lusis, Aldons J

Abstract

Most of the biological understanding of mechanisms underlying coronary artery disease (CAD) derives from studies of mouse models. The identification of multiple CAD loci and strong candidate genes in large human genome-wide association studies (GWASs) presented an opportunity to examine the relevance of mouse models for the human disease. We comprehensively reviewed the mouse literature, including 827 literature-derived genes, and compared it to human data. First, we observed striking concordance of risk factors for atherosclerosis in mice and humans. Second, there was highly significant overlap of mouse genes with human genes identified by GWASs. In particular, of the 46 genes with strong association signals in CAD GWASs that were studied in mouse models, all but one exhibited consistent effects on atherosclerosis-related phenotypes. Third, we compared 178 CAD-associated pathways derived from human GWASs with 263 from mouse studies and observed that the majority were consistent between the species.

Published
2017

6. Elucidation of the genetic causes of bicuspid aortic valve disease

Author

Gehlen, Jan, Stundl, Anja, Debiec, Radoslaw, Fontana, Federica, Krane, Markus, Sharipova, Dinara, Nelson, Christopher P., Al-Kassou, Baravan, Giel, Ann Sophie, Sinning, Jan Malte, Bruenger, Christopher M. H., Zelck, Carolin F., Koebbe, Laura L., Braund, Peter S., Webb, Thomas R., Hetherington, Simon, Ensminger, Stephan, Fujita, Buntaro, Mohamed, Salah A., Shrestha, Malakh, Krueger, Heike, Siepe, Matthias, Kari, Fabian Alexander, Nordbeck, Peter, Buravezky, Larissa, Kelm, Malte, Veulemans, Verena, Adam, Matti, Baldus, Stephan, Laugwitz, Karl Ludwig, Haas, Yannick, Karck, Matthias, Mehlhorn, Uwe, Conzelmann, Lars Oliver, Breitenbach, Ingo, Lebherz, Corinna, Urbanski, Paul, Kim, Won Keun, Kandels, Joscha, Ellinghaus, David, Nowak-Goettl, Ulrike, Hoffmann, Per, Wirth, Felix, Doppler, Stefanie, Lahm, Harald, Dressen, Martina, von Scheidt, Moritz, Knoll, Katharina, Kessler, Thorsten, Hengstenberg, Christian, Schunkert, Heribert, Nickenig, Georg, Noethen, Markus M., Bolger, Aidan P., Abdelilah-Seyfried, Salim, Samani, Nilesh J., Erdmann, Jeanette, Trenkwalder, Teresa, Schumacher, Johannes, Gehlen, Jan, Stundl, Anja, Debiec, Radoslaw, Fontana, Federica, Krane, Markus, Sharipova, Dinara, Nelson, Christopher P., Al-Kassou, Baravan, Giel, Ann Sophie, Sinning, Jan Malte, Bruenger, Christopher M. H., Zelck, Carolin F., Koebbe, Laura L., Braund, Peter S., Webb, Thomas R., Hetherington, Simon, Ensminger, Stephan, Fujita, Buntaro, Mohamed, Salah A., Shrestha, Malakh, Krueger, Heike, Siepe, Matthias, Kari, Fabian Alexander, Nordbeck, Peter, Buravezky, Larissa, Kelm, Malte, Veulemans, Verena, Adam, Matti, Baldus, Stephan, Laugwitz, Karl Ludwig, Haas, Yannick, Karck, Matthias, Mehlhorn, Uwe, Conzelmann, Lars Oliver, Breitenbach, Ingo, Lebherz, Corinna, Urbanski, Paul, Kim, Won Keun, Kandels, Joscha, Ellinghaus, David, Nowak-Goettl, Ulrike, Hoffmann, Per, Wirth, Felix, Doppler, Stefanie, Lahm, Harald, Dressen, Martina, von Scheidt, Moritz, Knoll, Katharina, Kessler, Thorsten, Hengstenberg, Christian, Schunkert, Heribert, Nickenig, Georg, Noethen, Markus M., Bolger, Aidan P., Abdelilah-Seyfried, Salim, Samani, Nilesh J., Erdmann, Jeanette, Trenkwalder, Teresa, and Schumacher, Johannes

Abstract

Aims The present study aims to characterize the genetic risk architecture of bicuspid aortic valve (BAV) disease, the most common congenital heart defect. Methods and results We carried out a genome-wide association study (GWAS) including 2236 BAV patients and 11 604 controls. This led to the identification of a new risk locus for BAV on chromosome 3q29. The single nucleotide polymorphism rs2550262 was genome-wide significant BAV associated (P = 3.49 x 10(-08)) and was replicated in an independent case-control sample. The risk locus encodes a deleterious missense variant in MUC4 (p.Ala4821Ser), a gene that is involved in epithelial-to-mesenchymal transformation. Mechanistical studies in zebrafish revealed that loss of Muc4 led to a delay in cardiac valvular development suggesting that loss of MUC4 may also play a role in aortic valve malformation. The GWAS also confirmed previously reported BAV risk loci at PALMD (P = 3.97 x 10(-16)), GATA4 (P = 1.61 x 10(-09)), and TEX41 (P = 7.68 x 10(-04)). In addition, the genetic BAV architecture was examined beyond the single-marker level revealing that a substantial fraction of BAV heritability is polygenic and similar to 20% of the observed heritability can be explained by our GWAS data. Furthermore, we used the largest human single-cell atlas for foetal gene expression and show that the transcriptome profile in endothelial cells is a major source contributing to BAV pathology. Conclusion Our study provides a deeper understanding of the genetic risk architecture of BAV formation on the single marker and polygenic level.

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