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2. Alveolar macrophage-expressed Plet1 is a driver of lung epithelial repair after viral pneumonia

Author

Pervizaj-Oruqaj, Learta, Selvakumar, Balachandar, Ferrero, Maximiliano Ruben, Heiner, Monika, Malainou, Christina, Glaser, Rolf David, Wilhelm, Jochen, Bartkuhn, Marek, Weiss, Astrid, Alexopoulos, Ioannis, Witte, Biruta, Gattenlöhner, Stefan, Vadász, István, Morty, Rory Edward, Seeger, Werner, Schermuly, Ralph Theo, Vazquez-Armendariz, Ana Ivonne, and Herold, Susanne

Published
2024
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5. Myofibroblasts emerge during alveolar regeneration following influenza-virus-induced lung injury

Author

Khadim, Ali, Kiliaris, Georgios, Vazquez-Armendariz, Ana Ivonne, Procida-Kowalski, Tara, Glaser, David, Bartkuhn, Marek, Malik, Tanya, Chu, Xuran, Moiseenko, Alena, Kuznetsova, Irina, Ahmadvand, Negah, Lingampally, Arun, Hadzic, Stefan, Alexopoulos, Ioannis, Chen, Yuexin, Günther, Andreas, Behr, Jürgen, Neumann, Jens, Schiller, Herbert B., Li, Xiaokun, Weissmann, Norbert, Braun, Thomas, Seeger, Werner, Wygrecka, Malgorzata, Morty, Rory E., Herold, Susanne, and El Agha, Elie

Published
2025
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7. Association of Phosphodiesterase-5 Inhibitor Treatment With Improved Survival in Pulmonary Hypertension Associated With COPD in the Pulmonary Vascular Research Institute GoDeep Meta-Registry

Author

Tello, Khodr, Yogeswaran, Athiththan, Majeed, Raphael W., Kiely, David G., Lawrie, Allan, Brittain, Evan, Annis, Jeffrey S., Olschewski, Horst, Kovacs, Gabor, Hassoun, Paul M., Balasubramanian, Aparna, Konswa, Ziad, Sweatt, Andrew J., Zamanian, Roham T., Wilkins, Martin R., Howard, Luke, Arvanitaki, Alexandra, Giannakoulas, George, Cajigas, Hector R., Frantz, Robert, Williams, Paul G., Frauendorf, Marlize, Marquardt, Kurt, Antoine, Tobiah, Fuenderich, Meike, Richter, Manuel, Grimminger, Friedrich, Ghofrani, Hossein-Ardeschir, Wilhelm, Jochen, and Seeger, Werner

Published
2025
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8. Analysis of acute COVID-19 including chronic morbidity: protocol for the deep phenotyping National Pandemic Cohort Network in Germany (NAPKON-HAP)

Author

Steinbeis, Fridolin, Thibeault, Charlotte, Steinbrecher, Sarah, Ahlgrimm, Yvonne, Haack, Ira an, August, Dietrich, Balzuweit, Beate, Bellinghausen, Carla, Berger, Sarah, Chaplinskaya-Sobol, Irina, Cornely, Oliver, Doeblin, Patrick, Endres, Matthias, Fink, Claudia, Finke, Carsten, Frank, Sandra, Hanß, Sabine, Hartung, Tim, Hellmuth, Johannes Christian, Herold, Susanne, Heuschmann, Peter, Heyckendorf, Jan, Heyder, Ralf, Hippenstiel, Stefan, Hoffmann, Wolfgang, Kelle, Sebastian Ulrich, Knape, Philipp, Koehler, Philipp, Kretzler, Lucie, Leistner, David Manuel, Lienau, Jasmin, Lorbeer, Roberto, Lorenz-Depiereux, Bettina, Lüttke, Constanze Dorothea, Mai, Knut, Merle, Uta, Meyer-Arndt, Lil Antonia, Miljukov, Olga, Muenchhoff, Maximilian, Müller-Plathe, Moritz, Neuhann, Julia, Neuhauser, Hannelore, Nieters, Alexandra, Otte, Christian, Pape, Daniel, Pinto, Rafaela Maria, Pley, Christina, Pudszuhn, Annett, Reuken, Philipp, Rieg, Siegberg, Ritter, Petra, Rohde, Gernot, Rönnefarth, Maria, Ruzicka, Michael, Schaller, Jens, Schmidt, Anne, Schmidt, Sein, Schwachmeyer, Verena, Schwanitz, Georg, Seeger, Werner, Stahl, Dana, Stobäus, Nicole, Stubbe, Hans Christian, Suttorp, Norbert, Temmesfeld, Bettina, Thun, Sylvia, Triller, Paul, Trinkmann, Frederik, Vadasz, Istvan, Valentin, Heike, Vehreschild, Maria, von Kalle, Christof, von Lilienfeld-Toal, Marie, Weber, Joachim, Welte, Tobias, Wildberg, Christian, Wizimirski, Robert, Zvork, Saskia, Sander, Leif Erik, Vehreschild, Janne, Zoller, Thomas, Kurth, Florian, and Witzenrath, Martin

Published
2024
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9. Abstract 4118178: Echocardiographic Measure of Right Ventricular-Pulmonary Arterial Coupling Predicts Survival in Lung Cancer

Author

Rako, Zvonimir, Cekay, Michael, Yogeswaran, Athiththan, Yildiz, Selin, Arndt, Philipp Friedrich, Kremer, Nils, Schaefer, Simon, Janetzko, Patrick, Brito da Rocha, Bruno, Mummert, Chris, Franken, Johanna, Soethe, Henrik, Werner, Hannah, Dumitrascu, Rio, Grimminger, Friedrich, Ghofrani, Ardeschir, Savai Pullamsetti, Soni, Seeger, Werner, Naeije, Robert, Savai, Rajkumar, Eul, Bastian, and Tello, Khodr

Published
2024
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10. Evaluation of a medical student-delivered smoking prevention program utilizing a face-aging mobile app for secondary schools in Germany: The Education Against Tobacco cluster-randomized controlled trial

Author

Brinker, Titus J., Krieghoff-Henning, Eva I., Suhre, Janina L., Silchmüller, Marc Phillipp, Divizieva, Evgenia, Wilhelm, Jilada, Hillebrand, Gabriel, Haney, Ailís C., Srivastava, Aayushi, Haney, Caelán M., Seeger, Werner, Penka, Dominik, Gall, Henning, Gaim, Benedikt, Glisic, Lazar, Stark, Tobias, Swoboda, Susanne M., Baumermann, Sonja, Brieske, Christian M., Jakob, Lena, Fahrner, Hannah Maria, Anhuef, Ole, Schmidt, Selina Marisa, Alfitian, Jonas, Taha, Lava, Beißwenger, Hanna, Groneberg, David A., Thomas, Roger E., Fröhling, Stefan, von Kalle, Christof, Baudson, Tanja Gabriele, Buslaff, Fabian, and Mons, Ute

Published
2024
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11. Comparison of Contemporary Risk Scores in All Groups of Pulmonary Hypertension: A Pulmonary Vascular Research Institute GoDeep Meta-Registry Analysis

Author

Antoine, Tobiah, Backofen, Achim, Cannon, John, Damonte, Victoria, Echazarreta, Diego, Eichstaedt, Christina, Elwing, Jean, Förster, Kai, Gruenig, Ekkehard, Hilgendorff, Anne, Jose, Arun, Junaeda, Ernesto, Krieb, Philipp, Marquardt, Kurt, Osborn, Karen, Pepke-Zaba, Johanna, Tilea, Ioan, Varga, Andreea, Yogeswaran, Athiththan, Gall, Henning, Fünderich, Meike, Wilkins, Martin R., Howard, Luke, Kiely, David G., Lawrie, Allan, Hassoun, Paul M., Sirenklo, Yuriy, Torbas, Olena, Sweatt, Andrew J., Zamanian, Roham T., Williams, Paul G., Frauendorf, Marlize, Arvanitaki, Alexandra, Giannakoulas, George, Saleh, Khaled, Sabbour, Hani, Cajigas, Hector R., Frantz, Robert, Al Ghouleh, Imad, Chan, Stephen Y., Brittain, Evan, Annis, Jeffrey S., Pepe, Antonella, Ghio, Stefano, Orfanos, Stylianos, Anthi, Anastasia, Majeed, Raphael W., Wilhelm, Jochen, Ghofrani, Hossein Ardeschir, Richter, Manuel J., Grimminger, Friedrich, Sahay, Sandeep, Tello, Khodr, and Seeger, Werner

Published
2024
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13. Transcriptional profiling unveils molecular subgroups of adaptive and maladaptive right ventricular remodeling in pulmonary hypertension

Author

Khassafi, Fatemeh, Chelladurai, Prakash, Valasarajan, Chanil, Nayakanti, Sreenath Reddy, Martineau, Sandra, Sommer, Natascha, Yokokawa, Tetsuro, Boucherat, Olivier, Kamal, Aryan, Kiely, David G., Swift, Andrew J., Alabed, Samer, Omura, Junichi, Breuils-Bonnet, Sandra, Kuenne, Carsten, Potus, Francois, Günther, Stefan, Savai, Rajkumar, Seeger, Werner, Looso, Mario, Lawrie, Allan, Zaugg, Judith B., Tello, Khodr, Provencher, Steeve, Bonnet, Sébastien, and Pullamsetti, Soni Savai

Published
2023
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17. Noncanonical HIPPO/MST Signaling via BUB3 and FOXO Drives Pulmonary Vascular Cell Growth and Survival

Author

Kudryashova, Tatiana V, Dabral, Swati, Nayakanti, Sreenath, Ray, Arnab, Goncharov, Dmitry A, Avolio, Theodore, Shen, Yuanjun, Rode, Analise, Pena, Andressa, Jiang, Lifeng, Lin, Derek, Baust, Jeffrey, Bachman, Timothy N, Graumann, Johannes, Ruppert, Clemens, Guenther, Andreas, Schmoranzer, Mario, Grobs, Yann, Lemay, Sarah Eve, Tremblay, Eve, Breuils-Bonnet, Sandra, Boucherat, Olivier, Mora, Ana L, DeLisser, Horace, Zhao, Jing, Zhao, Yutong, Bonnet, Sébastien, Seeger, Werner, Pullamsetti, Soni S, and Goncharova, Elena A

Subjects
Medical Physiology, Biomedical and Clinical Sciences, Lung, Rare Diseases, 2.1 Biological and endogenous factors, Aetiology, Cardiovascular, Animals, Cell Cycle Proteins, Cell Proliferation, Cells, Cultured, Chromosomal Proteins, Non-Histone, Forkhead Transcription Factors, Hypertension, Pulmonary, Hypoxia, Mammals, Mechanistic Target of Rapamycin Complex 1, Mice, Myocytes, Smooth Muscle, Poly-ADP-Ribose Binding Proteins, Proteomics, Proto-Oncogene Proteins c-akt, Pulmonary Arterial Hypertension, Pulmonary Artery, Vascular Remodeling, animals, hypoxia, mice, proteomic, pulmonary artery, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences
Abstract

RationaleThe MSTs (mammalian Ste20-like kinases) 1/2 are members of the HIPPO pathway that act as growth suppressors in adult proliferative diseases. Pulmonary arterial hypertension (PAH) manifests by increased proliferation and survival of pulmonary vascular cells in small PAs, pulmonary vascular remodeling, and the rise of pulmonary arterial pressure. The role of MST1/2 in PAH is currently unknown.ObjectiveTo investigate the roles and mechanisms of the action of MST1 and MST2 in PAH.Methods and resultsUsing early-passage pulmonary vascular cells from PAH and nondiseased lungs and mice with smooth muscle-specific tamoxifen-inducible Mst1/2 knockdown, we found that, in contrast to canonical antiproliferative/proapoptotic roles, MST1/2 act as proproliferative/prosurvival molecules in human PAH pulmonary arterial vascular smooth muscle cells and pulmonary arterial adventitial fibroblasts and support established pulmonary vascular remodeling and pulmonary hypertension in mice with SU5416/hypoxia-induced pulmonary hypertension. By using unbiased proteomic analysis, gain- and loss-of function approaches, and pharmacological inhibition of MST1/2 kinase activity by XMU-MP-1, we next evaluated mechanisms of regulation and function of MST1/2 in PAH pulmonary vascular cells. We found that, in PAH pulmonary arterial adventitial fibroblasts, the proproliferative function of MST1/2 is caused by IL-6-dependent MST1/2 overexpression, which induces PSMC6-dependent downregulation of forkhead homeobox type O 3 and hyperproliferation. In PAH pulmonary arterial vascular smooth muscle cells, MST1/2 acted via forming a disease-specific interaction with BUB3 and supported ECM (extracellular matrix)- and USP10-dependent BUB3 accumulation, upregulation of Akt-mTORC1, cell proliferation, and survival. Supporting our in vitro observations, smooth muscle-specific Mst1/2 knockdown halted upregulation of Akt-mTORC1 in small muscular PAs of mice with SU5416/hypoxia-induced pulmonary hypertension.ConclusionsTogether, this study describes a novel proproliferative/prosurvival role of MST1/2 in PAH pulmonary vasculature, provides a novel mechanistic link from MST1/2 via BUB3 and forkhead homeobox type O to the abnormal proliferation and survival of pulmonary arterial vascular smooth muscle cells and pulmonary arterial adventitial fibroblasts, remodeling and pulmonary hypertension, and suggests new target pathways for therapeutic intervention.

Published
2022

19. Defining the clinical validity of genes reported to cause pulmonary arterial hypertension

Author

Callejo, Emily P., Day, Kristina M., Macaya, Daniela, Maldonado-Velez, Gabriel, Archer, Stephen L., Auckland, Kathryn, Austin, Eric D., Badagliacca, Roberto, Barberà, Joan-Albert, Belge, Catharina, Bogaard, Harm Jan, Bonnet, Sébastien, Boomars, Karin A., Boucherat, Olivier, Chakinala, Murali M., Condliffe, Robin, Damico, Rachel Lynn, Delcroix, Marion, Desai, Ankit A., Doboszynska, Anna, Elliott, C. Greg, Eyries, Melanie, Escribano Subías, Maria Pilar, Gall, Henning, Ghio, Stefano, Ghofrani, Ardeschir-Hossein, Grünig, Ekkehard, Hamid, Rizwan, Harbaum, Lars, Hassoun, Paul M., Hemnes, Anna R., Hinderhofer, Katrin, Howard, Luke S., Humbert, Marc, Kiely, David G., Langleben, David, Lawrie, Allan, Loyd, Jim E., Moledina, Shahin, Montani, David, Morrell, Nichols W., Nichols, William C., Olschewski, Andrea, Olschewski, Horst, Papa, Silvia, Pauciulo, Mike W., Provencher, Steve, Quarck, Rozenn, Rhodes, Christopher J., Scelsi, Laura, Seeger, Werner, Stewart, Duncan J., Sweatt, Andrew, Swietlik, Emilia M., Treacy, Carmen, Trembath, Richard C., Tura-Ceide, Olga, Vizza, Carmine Dario, Vonk Noordegraaf, Anton, Wilkins, Martin R., Zamanian, Roham T., Zateyshchikov, Dmitry, Welch, Carrie L., Aldred, Micheala A., Balachandar, Srimmitha, Dooijes, Dennis, Eichstaedt, Christina A., Gräf, Stefan, Houweling, Arjan C., Machado, Rajiv D., Pandya, Divya, Prapa, Matina, Shaukat, Memoona, Southgate, Laura, Tenorio-Castano, Jair, and Chung, Wendy K.

Published
2023
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21. CXCL10 deficiency limits macrophage infiltration, preserves lung matrix, and enables lung growth in bronchopulmonary dysplasia

Author

Hirani, Dharmesh V., Thielen, Florian, Mansouri, Siavash, Danopoulos, Soula, Vohlen, Christina, Haznedar-Karakaya, Pinar, Mohr, Jasmine, Wilke, Rebecca, Selle, Jaco, Grosch, Thomas, Mizik, Ivana, Odenthal, Margarete, Alvira, Cristina M., Kuiper-Makris, Celien, Pryhuber, Gloria S., Pallasch, Christian, van Koningsbruggen-Rietschel, S., Al-Alam, Denise, Seeger, Werner, Savai, Rajkumar, Dötsch, Jörg, and Alejandre Alcazar, Miguel A.

Published
2023
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23. Imaging the right atrium in pulmonary hypertension: A systematic review and meta-analysis

Author

Richter, Manuel J., Fortuni, Federico, Alenezi, Fawaz, D'Alto, Michele, Badagliacca, Roberto, Brunner, Nathan W., van Dijk, Arie P., Douschan, Philipp, Gall, Henning, Ghio, Stefano, Giudice, Francesco Lo, Grünig, Ekkehard, Haddad, Francois, Howard, Luke, Rajagopal, Sudarshan, Stens, Niels, Stolfo, Davide, Thijssen, Dick H.J., Vizza, Carmine Dario, Zamanian, Roham T., Zhong, Liang, Seeger, Werner, Ghofrani, Hossein A., and Tello, Khodr

Published
2023
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24. ADPGK‐AS1 long noncoding RNA switches macrophage metabolic and phenotypic state to promote lung cancer growth

Author

Karger, Annika, Mansouri, Siavash, Leisegang, Matthias S, Weigert, Andreas, Günther, Stefan, Kuenne, Carsten, Wittig, Ilka, Zukunft, Sven, Klatt, Stephan, Aliraj, Blerina, Klotz, Laura V, Winter, Hauke, Mahavadi, Poornima, Fleming, Ingrid, Ruppert, Clemens, Witte, Biruta, Alkoudmani, Ibrahim, Gattenlöhner, Stefan, Grimminger, Friedrich, Seeger, Werner, Pullamsetti, Soni Savai, and Savai, Rajkumar

Published
2023
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28. Case Series Evaluating the Relationship of SGLT2 Inhibition to Pulmonary Artery Pressure and Non-Invasive Cardiopulmonary Parameters in HFpEF/HFmrEF Patients—A Pilot Study.

Author

Herrmann, Ester Judith, Guckert, Michael, Gruen, Dimitri, Keller, Till, Tello, Khodr, Seeger, Werner, Sossalla, Samuel, and Assmus, Birgit

Subjects
PULMONARY artery, VASCULAR resistance, HEART failure, CARDIAC output, CARDIAC catheterization
Abstract

The initiation of sodium–glucose cotransporter 2 (SGLT2) inhibitor treatment was shown to reduce pulmonary artery pressure (PAP) in New York Heart Association (NYHA) class III heart failure (HF) patients with an implanted PAP sensor. We aimed to investigate the impact of SGLT2-I initiation on pulmonary vascular resistance (PVR), pulmonary capillary wedge pressure (PCWP), pulmonary arterial capacitance (PAC), and right ventricle (RV) to PA (RV-PA) coupling in a pilot cohort of HF with preserved/mildly reduced ejection fraction (HFpEF/HFmrEF) patients and whether PVR and PCWP can be serially calculated non-invasively using PAP sensor data during follow-up. Methods: Right heart catheterization parameters (PVR, PCWP, and PAC) were obtained at sensor implantation and echocardiographic assessments (E/E', RV-PA coupling, and RV cardiac output) were made at baseline and every 3 months. SGLT2 inhibition was initiated after 3 months of telemedical care. Three methods for calculating PVR and PCWP were compared using Bland–Altman plots and Spearman's correlation. Results: In 13 HF patients (mean age 77 ± 4 years), there were no significant changes in PAP, PVR, PCWP, RV-PA coupling, or PAC over 9 months (all p-values > 0.05), including after SGLT2-I initiation. PVR values were closely correlated across the three methods (PVRNew and PVRNew Tedford (r = 0.614, p < 0.001), PVREcho and PVRNew Tedford (r = 0.446, p = 0.006), and PVREcho and PVRNew (r = 0.394, p = 0.016)), but PCWP methods lacked reliable association (PCWPEcho and PCWPNew (r = 0.180, p = 0.332). Conclusions: No changes in cardiopulmonary hemodynamics were detected after hemodynamic telemonitoring either prior to or following SGLT2-I initiation. Different PVR assessment methods yielded comparable results, whereas PCWP methods were not associated with each other. Further investigations with larger cohorts including repeated right heart catheterization are planned. [ABSTRACT FROM AUTHOR]

Published
2025
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30. Genetic determinants of risk in pulmonary arterial hypertension: international genome-wide association studies and meta-analysis

Author

Rhodes, Christopher J, Batai, Ken, Bleda, Marta, Haimel, Matthias, Southgate, Laura, Germain, Marine, Pauciulo, Michael W, Hadinnapola, Charaka, Aman, Jurjan, Girerd, Barbara, Arora, Amit, Knight, Jo, Hanscombe, Ken B, Karnes, Jason H, Kaakinen, Marika, Gall, Henning, Ulrich, Anna, Harbaum, Lars, Cebola, Inês, Ferrer, Jorge, Lutz, Katie, Swietlik, Emilia M, Ahmad, Ferhaan, Amouyel, Philippe, Archer, Stephen L, Argula, Rahul, Austin, Eric D, Badesch, David, Bakshi, Sahil, Barnett, Christopher, Benza, Raymond, Bhatt, Nitin, Bogaard, Harm J, Burger, Charles D, Chakinala, Murali, Church, Colin, Coghlan, John G, Condliffe, Robin, Corris, Paul A, Danesino, Cesare, Debette, Stéphanie, Elliott, C Gregory, Elwing, Jean, Eyries, Melanie, Fortin, Terry, Franke, Andre, Frantz, Robert P, Frost, Adaani, Garcia, Joe GN, Ghio, Stefano, Ghofrani, Hossein-Ardeschir, Gibbs, J Simon R, Harley, John, He, Hua, Hill, Nicholas S, Hirsch, Russel, Houweling, Arjan C, Howard, Luke S, Ivy, Dunbar, Kiely, David G, Klinger, James, Kovacs, Gabor, Lahm, Tim, Laudes, Matthias, Machado, Rajiv D, Ross, Robert V MacKenzie, Marsolo, Keith, Martin, Lisa J, Moledina, Shahin, Montani, David, Nathan, Steven D, Newnham, Michael, Olschewski, Andrea, Olschewski, Horst, Oudiz, Ronald J, Ouwehand, Willem H, Peacock, Andrew J, Pepke-Zaba, Joanna, Rehman, Zia, Robbins, Ivan, Roden, Dan M, Rosenzweig, Erika B, Saydain, Ghulam, Scelsi, Laura, Schilz, Robert, Seeger, Werner, Shaffer, Christian M, Simms, Robert W, Simon, Marc, Sitbon, Olivier, Suntharalingam, Jay, Tang, Haiyang, Tchourbanov, Alexander Y, Thenappan, Thenappan, Torres, Fernando, Toshner, Mark R, Treacy, Carmen M, Noordegraaf, Anton Vonk, Waisfisz, Quinten, and Walsworth, Anna K

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Genetics, Human Genome, Lung, Aetiology, 2.1 Biological and endogenous factors, Cardiovascular, Female, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Genotyping Techniques, HLA-DP alpha-Chains, HLA-DP beta-Chains, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Pulmonary Arterial Hypertension, Risk Assessment, SOXF Transcription Factors, Signal Transduction, Survival Analysis, UK NIHR BioResource Rare Diseases Consortium, UK PAH Cohort Study Consortium, US PAH Biobank Consortium, Public Health and Health Services, Other Medical and Health Sciences, Cardiovascular medicine and haematology, Clinical sciences
Abstract

BackgroundRare genetic variants cause pulmonary arterial hypertension, but the contribution of common genetic variation to disease risk and natural history is poorly characterised. We tested for genome-wide association for pulmonary arterial hypertension in large international cohorts and assessed the contribution of associated regions to outcomes.MethodsWe did two separate genome-wide association studies (GWAS) and a meta-analysis of pulmonary arterial hypertension. These GWAS used data from four international case-control studies across 11 744 individuals with European ancestry (including 2085 patients). One GWAS used genotypes from 5895 whole-genome sequences and the other GWAS used genotyping array data from an additional 5849 individuals. Cross-validation of loci reaching genome-wide significance was sought by meta-analysis. Conditional analysis corrected for the most significant variants at each locus was used to resolve signals for multiple associations. We functionally annotated associated variants and tested associations with duration of survival. All-cause mortality was the primary endpoint in survival analyses.FindingsA locus near SOX17 (rs10103692, odds ratio 1·80 [95% CI 1·55-2·08], p=5·13 × 10-15) and a second locus in HLA-DPA1 and HLA-DPB1 (collectively referred to as HLA-DPA1/DPB1 here; rs2856830, 1·56 [1·42-1·71], p=7·65 × 10-20) within the class II MHC region were associated with pulmonary arterial hypertension. The SOX17 locus had two independent signals associated with pulmonary arterial hypertension (rs13266183, 1·36 [1·25-1·48], p=1·69 × 10-12; and rs10103692). Functional and epigenomic data indicate that the risk variants near SOX17 alter gene regulation via an enhancer active in endothelial cells. Pulmonary arterial hypertension risk variants determined haplotype-specific enhancer activity, and CRISPR-mediated inhibition of the enhancer reduced SOX17 expression. The HLA-DPA1/DPB1 rs2856830 genotype was strongly associated with survival. Median survival from diagnosis in patients with pulmonary arterial hypertension with the C/C homozygous genotype was double (13·50 years [95% CI 12·07 to >13·50]) that of those with the T/T genotype (6·97 years [6·02-8·05]), despite similar baseline disease severity.InterpretationThis is the first study to report that common genetic variation at loci in an enhancer near SOX17 and in HLA-DPA1/DPB1 is associated with pulmonary arterial hypertension. Impairment of SOX17 function might be more common in pulmonary arterial hypertension than suggested by rare mutations in SOX17. Further studies are needed to confirm the association between HLA typing or rs2856830 genotyping and survival, and to determine whether HLA typing or rs2856830 genotyping improves risk stratification in clinical practice or trials.FundingUK NIHR, BHF, UK MRC, Dinosaur Trust, NIH/NHLBI, ERS, EMBO, Wellcome Trust, EU, AHA, ACClinPharm, Netherlands CVRI, Dutch Heart Foundation, Dutch Federation of UMC, Netherlands OHRD and RNAS, German DFG, German BMBF, APH Paris, INSERM, Université Paris-Sud, and French ANR.

Published
2019

31. Identification of rare sequence variation underlying heritable pulmonary arterial hypertension.

Author

Gräf, Stefan, Haimel, Matthias, Bleda, Marta, Hadinnapola, Charaka, Southgate, Laura, Li, Wei, Hodgson, Joshua, Liu, Bin, Salmon, Richard M, Southwood, Mark, Machado, Rajiv D, Martin, Jennifer M, Treacy, Carmen M, Yates, Katherine, Daugherty, Louise C, Shamardina, Olga, Whitehorn, Deborah, Holden, Simon, Aldred, Micheala, Bogaard, Harm J, Church, Colin, Coghlan, Gerry, Condliffe, Robin, Corris, Paul A, Danesino, Cesare, Eyries, Mélanie, Gall, Henning, Ghio, Stefano, Ghofrani, Hossein-Ardeschir, Gibbs, J Simon R, Girerd, Barbara, Houweling, Arjan C, Howard, Luke, Humbert, Marc, Kiely, David G, Kovacs, Gabor, MacKenzie Ross, Robert V, Moledina, Shahin, Montani, David, Newnham, Michael, Olschewski, Andrea, Olschewski, Horst, Peacock, Andrew J, Pepke-Zaba, Joanna, Prokopenko, Inga, Rhodes, Christopher J, Scelsi, Laura, Seeger, Werner, Soubrier, Florent, Stein, Dan F, Suntharalingam, Jay, Swietlik, Emilia M, Toshner, Mark R, van Heel, David A, Vonk Noordegraaf, Anton, Waisfisz, Quinten, Wharton, John, Wort, Stephen J, Ouwehand, Willem H, Soranzo, Nicole, Lawrie, Allan, Upton, Paul D, Wilkins, Martin R, Trembath, Richard C, and Morrell, Nicholas W

Subjects
Humans, Genetic Predisposition to Disease, Transforming Growth Factor beta, Membrane Transport Proteins, Prognosis, Case-Control Studies, Signal Transduction, Gene Expression Regulation, Base Sequence, Mutation, Models, Molecular, Adult, Female, Male, Aquaporin 1, Bone Morphogenetic Protein Receptors, Type II, Adenosine Triphosphatases, Growth Differentiation Factors, SOXF Transcription Factors, HEK293 Cells, Familial Primary Pulmonary Hypertension, Whole Genome Sequencing, Bone Morphogenetic Protein Receptors, Type II, Models, Molecular
Abstract

Pulmonary arterial hypertension (PAH) is a rare disorder with a poor prognosis. Deleterious variation within components of the transforming growth factor-β pathway, particularly the bone morphogenetic protein type 2 receptor (BMPR2), underlies most heritable forms of PAH. To identify the missing heritability we perform whole-genome sequencing in 1038 PAH index cases and 6385 PAH-negative control subjects. Case-control analyses reveal significant overrepresentation of rare variants in ATP13A3, AQP1 and SOX17, and provide independent validation of a critical role for GDF2 in PAH. We demonstrate familial segregation of mutations in SOX17 and AQP1 with PAH. Mutations in GDF2, encoding a BMPR2 ligand, lead to reduced secretion from transfected cells. In addition, we identify pathogenic mutations in the majority of previously reported PAH genes, and provide evidence for further putative genes. Taken together these findings contribute new insights into the molecular basis of PAH and indicate unexplored pathways for therapeutic intervention.

Published
2018

32. Immunogenicity and reactogenicity of homologous mRNA-based and vector-based SARS-CoV-2 vaccine regimens in patients receiving maintenance dialysis

Author

Karakizlis, Hristos, Nahrgang, Christian, Strecker, Kevin, Chen, Jiangping, Aly, Mostafa, Slanina, Heiko, Schüttler, Christian G., Esso, Isla, Wolter, Martin, Todorova, Darina, Jessen, Sönke, Adamik, Andrea, Ronco, Claudio, Seeger, Werner, Weimer, Rolf, Sester, Martina, Birk, Horst-Walter, and Husain-Syed, Faeq

Published
2022
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35. Kidney Biopsy Findings in Patients with SARS-CoV-2 Infection or After COVID-19 Vaccination

Author

de las Mercedes Noriega, Maria, Husain-Syed, Faeq, Wulf, Sonia, Csala, Benjamin, Krebs, Christian F., Jabs, Wolfram J., Zipfel, Peter F., Gröne, Hermann-Josef, Wiech, Thorsten, Aedtner, Frank, Bačinović, Mustafa, Bartel-Kuss, Susanne, Bauer, Alexander, Beige, Joachim, Birk, Horst-Walter, Böll, Bernhard, Brylka, Philipp, Clasen, Wolfgang, Dasdelen, Süha, Eicher, Maria-Magdalena, Elnaggar, Amr, Farid, Alexander, Francois, Johannes, Gerth, Jens, Helmke, Annette, Hepburn, Helen, Hollenbeck, Markus, Huber, Tobias B., Jennert, Birgit, Jüttner, Christoph, Khaled, Akel, Kobayashi, Kazuhiro, Koop, Monika, Kuczkowski, Kamil, Loyen, Martin, Mahmud, Maida, Marczynski, Cornelia, Meyer, Tobias N., Nitschke, Martin, Reiter, Michael A., Ronco, Claudio, Schleucher, Norbert, Schmerler, Diana, Schmidt, Elisa Alba, Schmidt, Rüdiger, Schmitz, Michael, Seeger, Werner, Selbach, Jochen, Sellin, Lorenz, Srugies, Fabian, Swiecicka, Agnieszka, von Vietinghoff, Sibylle, Weinberg, Clemens, Wenzel, Ulrich, and Werth, Stephan Christian

Published
2023
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36. Fibrocytes boost tumor-supportive phenotypic switches in the lung cancer niche via the endothelin system

Author

Weigert, Andreas, Zheng, Xiang, Nenzel, Alina, Turkowski, Kati, Günther, Stefan, Strack, Elisabeth, Sirait-Fischer, Evelyn, Elwakeel, Eiman, Kur, Ivan M., Nikam, Vandana S., Valasarajan, Chanil, Winter, Hauke, Wissgott, Alexander, Voswinkel, Robert, Grimminger, Friedrich, Brüne, Bernhard, Seeger, Werner, Pullamsetti, Soni Savai, and Savai, Rajkumar

Published
2022
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38. Maternal and perinatal obesity induce bronchial obstruction and pulmonary hypertension via IL-6-FoxO1-axis in later life

Author

Selle, Jaco, Dinger, Katharina, Jentgen, Vanessa, Zanetti, Daniela, Will, Johannes, Georgomanolis, Theodoros, Vohlen, Christina, Wilke, Rebecca, Kojonazarov, Baktybek, Klymenko, Oleksiy, Mohr, Jasmine, v. Koningsbruggen-Rietschel, Silke, Rhodes, Christopher J., Ulrich, Anna, Hirani, Dharmesh, Nestler, Tim, Odenthal, Margarete, Mahabir, Esther, Nayakanti, Sreenath, Dabral, Swati, Wunderlich, Thomas, Priest, James, Seeger, Werner, Dötsch, Jörg, Pullamsetti, Soni S., and Alejandre Alcazar, Miguel A.

Published
2022
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42. Author Correction: Deficiency of Axl aggravates pulmonary arterial hypertension via BMPR2

Author

Novoyatleva, Tatyana, Rai, Nabham, Kojonazarov, Baktybek, Veeroju, Swathi, Ben-Batalla, Isabel, Caruso, Paola, Shihan, Mazen, Presser, Nadine, Götz, Elsa, Lepper, Carina, Herpel, Sebastian, Manaud, Grégoire, Perros, Frédéric, Gall, Henning, Ghofrani, Hossein Ardeschir, Weissmann, Norbert, Grimminger, Friedrich, Wharton, John, Wilkins, Martin, Upton, Paul D., Loges, Sonja, Morrell, Nicholas W., Seeger, Werner, and Schermuly, Ralph T.

Published
2022
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44. GLI1+ cells are a source of repair-supportive mesenchymal cells (RSMCs) during airway epithelial regeneration

Author

Chu, Xuran, Lingampally, Arun, Moiseenko, Alena, Kheirollahi, Vahid, Vazquez-Armendariz, Ana Ivonne, Koepke, Janine, Khadim, Ali, Kiliaris, Georgios, Shahriari Felordi, Mahtab, Zabihi, Mahsa, Shalashova, Irina, Alexopoulos, Ioannis, Günther, Stefan, Lebrigand, Kevin, Truchi, Marin, Günther, Andreas, Braun, Thomas, Mari, Bernard, Samakovlis, Christos, Li, Xiaokun, Seeger, Werner, Herold, Susanne, Zhang, Jin-San, Bellusci, Saverio, and El Agha, Elie

Published
2022
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47. Exercise Limitation in Pulmonary Hypertension – Physiological Insights into the 6-Minute Walk Test.

Author

Kremer, Nils, Schaefer, Simon, Yogeswaran, Athiththan, Rako, Zvonimir, Ghofrani, Hossein-Ardeschir, Seeger, Werner, Kojonazarov, Baktybek, Heerdt, Paul M., Tedford, Ryan J., and Tello, Khodr

Subjects
BRAIN natriuretic factor, DIASTOLIC blood pressure, AEROBIC capacity, VENOUS pressure, SYSTOLIC blood pressure
Abstract

The document discusses a study on right ventricular-pulmonary arterial (RV-PA) coupling dynamics and their impact on exercise capacity in patients with pulmonary hypertension (PH) during the 6-minute walk test (6MWT). The study found that maintaining RV-PA coupling during exercise is crucial for 6MWT performance in PH patients, with uncoupling leading to decreased exercise capacity. The research highlights the importance of contractile reserve and the potential impact of RV function on real-world exercise capacity in PH patients. The study acknowledges limitations, such as the small sample size and the use of a pressure-only method for calculating RV-PA coupling during the 6MWT. [Extracted from the article]

Published
2024
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48. Glycosylation signature of plasma IgA of critically ill COVID-19 patients.

Author

Potaczek, Daniel P., van Tol, Bianca D. M., Falck, David, Krolczik, Christina, Zlatina, Kristina, Bertrams, Wilhelm, Wilhelm, Jochen, Schmeck, Bernd, Seeliger, Benjamin, David, Sascha, Skevaki, Chrysanthi, Mack, Elisabeth, Seeger, Werner, Schaefer, Liliana, Galuska, Sebastian P., Wuhrer, Manfred, and Wygrecka, Małgorzata

Subjects
COVID-19 pandemic, ADULT respiratory distress syndrome, COVID-19, COMMUNICABLE diseases, IMMUNE response
Abstract

Thromboembolic complications are common in severe COVID-19 and are thought to result from excessive neutrophil-extracellular-trap (NET)-driven immunothrombosis. Glycosylation plays a vital role in the efficiency of immunoglobulin A (IgA) effector functions, with significant implications for NET formation in infectious diseases. This study represents the first comprehensive analysis of plasma IgA glycosylation during severe SARS-CoV-2 or Influenza A infection, revealing lower sialylation and higher galactosylation of IgA1 O-glycans in acute respiratory distress syndrome (ARDS), regardless of the underlying cause of the disease. Importantly, N-glycans displayed an infection-specific pattern, with N47 of IgA2 showing diminished sialylation and bisection, and N340/N327 of IgA1/2 demonstrating lower fucosylation and antennarity along with higher non-complex glycans in COVID-19 compared to Influenza. Notably, COVID-19 IgA possessed strong ability to induce NET formation and its glycosylation patterns correlated with extracellular DNA levels in plasma of critically ill COVID-19 patients. Our data underscores the necessity of further research on the role of IgA glycosylation in the modulation of pathogen-specific immune responses in COVID-19 and other infectious diseases. [ABSTRACT FROM AUTHOR]

Published
2024
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