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428 results on '"Bogaard, Harm J."'

1. Biomarker Analysis Provides Evidence for Host Response Homogeneity in Patients With COVID-19

Author

van Agtmael, Michiel A., Algera, Anne G., Appelman, Brent, van Baarle, Floor E.H.P., van de Beek, Diederik, Beudel, Martijn, Bogaard, Harm J., Bos, Lieuwe D.J., Botta, Michela, de Brabander, Justin, de Bree, Godelieve J., Brouwer, Matthijs C., de Bruin, Sanne, Bugiani, Marianna, Bulle, Esther B., Chouchane, Osoul, Cloherty, Alex P.M., Buis, David, de Rotte, Maurtis C.F.J., Dijkstra, Mirjam, Dongelmans, Dave A., Dujardin, Romein W.G., Elbers, Paul E., Fleuren, Lucas M., Geerlings, Suzanne E., Geijtenbeek, Theo B.H., Girbes, Armand R.J., Goorhuis, Bram, Grobusch, Martin P., Hagens, Laura A., Hamann, Jorg, Harris, Vanessa C., Hemke, Robert, Hermans, Sabine M., Heunks, Leo M.A., Hollmann, Markus W., Horn, Janneke, Hovius, Joppe W., de Jong, Menno D., Koning, Rutger, Lim, Endry H.T., van Mourik, Niels, Nellen, Jeannine F., Nossent, Esther J., Paulus, Frederique, Peters, Edgar, Piña-Fuentes, Dan, van der Poll, Tom, Preckel, Bennedikt, Raasveld, Jorinde, Reijnders, Tom D.Y., Schinkel, Michiel, Schrauwen, Femke A.P., Schultz, Marcus J., Schuurman, Alex R., Schuurmans, Jaap, Sigaloff, Kim, Slim, Marleen A., Smeele, Patrick, Smit, Marry R., Stijnis, Cornelis, Stilma, Willemke, Teunissen, Charlotte E., Thoral, Patrick, Tsonas, Anissa M., Tuinman, Pieter R., van der Valk, Marc, Veelo, Denise P., Vlaar, Alexander P.J., Volleman, Carolien, de Vries, Heder, van Vught, Lonneke A., van Vugt, Michèle, Wiersinga, Joost, Wouters, Dorien, Zwinderman, Koos, van Amstel, Rombout B.E., Michels, Erik H.A., and Smeele, Patrick J.

Published
2024
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4. Hot topics in the mechanisms of pulmonary arterial hypertension disease: cancer‐like pathobiology, the role of the adventitia, systemic involvement, and right ventricular failure

Author

Spiekerkoetter, Edda, Goncharova, Elena A, Guignabert, Christophe, Stenmark, Kurt, Kwapiszewska, Grazyna, Rabinovitch, Marlene, Voelkel, Norbert, Bogaard, Harm J, Graham, Brian, Pullamsetti, Soni S, and Kuebler, Wolfgang M

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Lung, Rare Diseases, Aetiology, 2.1 Biological and endogenous factors, Cardiovascular, experimental pulmonary hypertension, Pro-Con debate, right ventricle function and dysfunction, vascular remodeling, Cardiorespiratory Medicine and Haematology, Cardiovascular medicine and haematology
Abstract

In order to intervene appropriately and develop disease-modifying therapeutics for pulmonary arterial hypertension, it is crucial to understand the mechanisms of disease pathogenesis and progression. We herein discuss four topics of disease mechanisms that are currently highly debated, yet still unsolved, in the field of pulmonary arterial hypertension. Is pulmonary arterial hypertension a cancer-like disease? Does the adventitia play an important role in the initiation of pulmonary vascular remodeling? Is pulmonary arterial hypertension a systemic disease? Does capillary loss drive right ventricular failure? While pulmonary arterial hypertension does not replicate all features of cancer, anti-proliferative cancer therapeutics might still be beneficial in pulmonary arterial hypertension if monitored for safety and tolerability. It was recognized that the adventitia as a cell-rich compartment is important in the disease pathogenesis of pulmonary arterial hypertension and should be a therapeutic target, albeit the data are inconclusive as to whether the adventitia is involved in the initiation of neointima formation. There was agreement that systemic diseases can lead to pulmonary arterial hypertension and that pulmonary arterial hypertension can have systemic effects related to the advanced lung pathology, yet there was less agreement on whether idiopathic pulmonary arterial hypertension is a systemic disease per se. Despite acknowledging the limitations of exactly assessing vascular density in the right ventricle, it was recognized that the failing right ventricle may show inadequate vascular adaptation resulting in inadequate delivery of oxygen and other metabolites. Although the debate was not meant to result in a definite resolution of the specific arguments, it sparked ideas about how we might resolve the discrepancies by improving our disease modeling (rodent models, large-animal studies, studies of human cells, tissues, and organs) as well as standardization of the models. Novel experimental approaches, such as lineage tracing and better three-dimensional imaging of experimental as well as human lung and heart tissues, might unravel how different cells contribute to the disease pathology.

Published
2019

5. Biallelic variants in the calpain regulatory subunit CAPNS1 cause pulmonary arterial hypertension

Author

Postma, Alex V., Rapp, Christina K., Knoflach, Katrin, Volk, Alexander E., Lemke, Johannes R., Ackermann, Maximilian, Regamey, Nicolas, Latzin, Philipp, Celant, Lucas, Jansen, Samara M.A., Bogaard, Harm J., Ilgun, Aho, Alders, Mariëlle, van Spaendonck-Zwarts, Karin Y., Jonigk, Danny, Klein, Christoph, Gräf, Stefan, Kubisch, Christian, Houweling, Arjan C., and Griese, Matthias

Published
2023
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6. 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

7. Assessment of Right Ventricular Function in the Research Setting: Knowledge Gaps and Pathways Forward. An Official American Thoracic Society Research Statement

Author

Lahm, Tim, Douglas, Ivor S, Archer, Stephen L, Bogaard, Harm J, Chesler, Naomi C, Haddad, Francois, Hemnes, Anna R, Kawut, Steven M, Kline, Jeffrey A, Kolb, Todd M, Mathai, Stephen C, Mercier, Olaf, Michelakis, Evangelos D, Naeije, Robert, Tuder, Rubin M, Ventetuolo, Corey E, Vieillard-Baron, Antoine, Voelkel, Norbert F, Vonk-Noordegraaf, Anton, and Hassoun, Paul M

Subjects
Cardiovascular, Heart Disease, Lung, Rare Diseases, Animals, Humans, Research, Societies, Medical, United States, Ventricular Dysfunction, Right, Ventricular Function, Right, right ventricle, pulmonary hypertension, pulmonary embolism, acute respiratory distress syndrome, pulmonary circulation, American Thoracic Society Assembly on Pulmonary Circulation, Medical and Health Sciences, Respiratory System
Abstract

BackgroundRight ventricular (RV) adaptation to acute and chronic pulmonary hypertensive syndromes is a significant determinant of short- and long-term outcomes. Although remarkable progress has been made in the understanding of RV function and failure since the meeting of the NIH Working Group on Cellular and Molecular Mechanisms of Right Heart Failure in 2005, significant gaps remain at many levels in the understanding of cellular and molecular mechanisms of RV responses to pressure and volume overload, in the validation of diagnostic modalities, and in the development of evidence-based therapies.MethodsA multidisciplinary working group of 20 international experts from the American Thoracic Society Assemblies on Pulmonary Circulation and Critical Care, as well as external content experts, reviewed the literature, identified important knowledge gaps, and provided recommendations.ResultsThis document reviews the knowledge in the field of RV failure, identifies and prioritizes the most pertinent research gaps, and provides a prioritized pathway for addressing these preclinical and clinical questions. The group identified knowledge gaps and research opportunities in three major topic areas: 1) optimizing the methodology to assess RV function in acute and chronic conditions in preclinical models, human studies, and clinical trials; 2) analyzing advanced RV hemodynamic parameters at rest and in response to exercise; and 3) deciphering the underlying molecular and pathogenic mechanisms of RV function and failure in diverse pulmonary hypertension syndromes.ConclusionsThis statement provides a roadmap to further advance the state of knowledge, with the ultimate goal of developing RV-targeted therapies for patients with RV failure of any etiology.

Published
2018

8. 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

10. Imatinib in patients with severe COVID-19: a randomised, double-blind, placebo-controlled, clinical trial

Author

Aman, Jurjan, Duijvelaar, Erik, Botros, Liza, Kianzad, Azar, Schippers, Job R, Smeele, Patrick J, Azhang, Sara, Bartelink, Imke H, Bayoumy, Ahmed A, Bet, Pierre M, Boersma, Wim, Bonta, Peter I, Boomars, Karin A T, Bos, Lieuwe D J, van Bragt, Job J M H, Braunstahl, Gert-Jan, Celant, Lucas R, Eger, Katrien A B, Geelhoed, J J Miranda, van Glabbeek, Yurika L E, Grotjohan, Hans P, Hagens, Laura A, Happe, Chris M, Hazes, Boaz D, Heunks, Leo M A, van den Heuvel, Michel, Hoefsloot, Wouter, Hoek, Rianne J A, Hoekstra, Romke, Hofstee, Herman M A, Juffermans, Nicole P, Kemper, E Marleen, Kos, Renate, Kunst, Peter W A, Lammers, Ariana, van der Lee, Ivo, van der Lee, E Laurien, Maitland-van der Zee, Anke-Hilse, Mau Asam, Pearl F M, Mieras, Adinda, Muller, Mirte, Neefjes, Elisabeth C W, Nossent, Esther J, Oswald, Laurien M A, Overbeek, Maria J, Pamplona, Carolina C, Paternotte, Nienke, Pronk, Niels, de Raaf, Michiel A, van Raaij, Bas F M, Reijrink, Merlijn, Schultz, Marcus J, Serpa Neto, Ary, Slob, Elise M A, Smeenk, Frank W J M, Smit, Marry R, Smits, A Josien, Stalenhoef, Janneke E, Tuinman, Pieter R, Vanhove, Arthur L E M, Wessels, Jeroen N, van Wezenbeek, Jessie C C, Vonk Noordegraaf, Anton, de Man, Frances S, and Bogaard, Harm J

Published
2021
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15. Constructing the Framework for Disease Modification in Pulmonary Arterial Hypertension.

Author

Zamanian, Roham T., Weatherald, Jason, Sweatt, Andrew J., Hemnes, Anna, Rashid, Moira, Psotka, Mitchell A., Bogaard, Harm J., and de Jesus Perez, Vinicio

Subjects
PULMONARY arterial hypertension, LUNG diseases, CRITICAL care medicine, ALZHEIMER'S disease, PULMONARY hypertension
Abstract

The article discusses the concept of disease modification in pulmonary arterial hypertension (PAH) and proposes a framework for its definition and evaluation in clinical trials. It defines disease modification as therapy-induced changes in clinical manifestations, disease trajectory, and outcomes due to an effect on the underlying pathophysiology. It proposes a randomized-withdrawal trial design to evaluate disease-modifying therapies effectively.

Published
2024
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16. Evaluating the technical use of a Fitbit during an intervention for patients with pulmonary arterial hypertension with quality of life as primary endpoint: Lessons learned from the UPHILL study.

Author

Kwant, Chermaine T., de Man, Frances S., Bogaard, Harm J., and Noordegraaf, Anton Vonk

Subjects
PULMONARY arterial hypertension, QUALITY of life, PULMONARY hypertension, PHYSICAL activity, ACTIVITIES of daily living
Abstract

This article examines technical use of Fitbit during an intervention for pulmonary hypertension (PAH)‐patients. Technical issues with the device led to data being unavailable(37.5%). During intervention objective daily physical activity (DPA) decreased and subjective DPA increased. This emphasizes that an assessment of DPA in PAH requires incorporating both objective and subjective measurements. [ABSTRACT FROM AUTHOR]

Published
2024
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26. The diagnostic accuracy of lung ultrasound to determine PiCCO-derived extravascular lung water in invasively ventilated patients with COVID-19 ARDS

Author

Atmowihardjo, Leila N., primary, Schippers, Job R., additional, Haaksma, Mark E., additional, Smit, Marry R., additional, Bogaard, Harm J., additional, Heunks, Leo, additional, Juffermans, Nicole P., additional, Schultz, Marcus J., additional, Endeman, Henrik, additional, Velzen, Patricia van, additional, Tuinman, Pieter R., additional, Aman, Jurjan, additional, and Bos, Lieuwe D. J., additional

Published
2023
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27. Cystic fibrosis transmembrane conductance regulator modulators attenuate platelet activation and aggregation in blood of healthy donors and COVID-19 patients

Author

Asmus, Erik, primary, Karle, Weronika, additional, Brack, Markus C., additional, Wittig, Corey, additional, Behrens, Felix, additional, Reinshagen, Leander, additional, Pfeiffer, Moritz, additional, Schulz, Sabrina, additional, Mandzimba-Maloko, Bertina, additional, Erfinanda, Lasti, additional, Perret, Paul L., additional, Michalick, Laura, additional, Smeele, Patrick J., additional, Lim, Endry H.T., additional, van den Brom, Charissa E., additional, Vonk, Alexander B.A., additional, Kaiser, Toralf, additional, Suttorp, Norbert, additional, Hippenstiel, Stefan, additional, Sander, Leif E., additional, Kurth, Florian, additional, Rauch, Ursula, additional, Landmesser, Ulf, additional, Haghikia, Arash, additional, Preissner, Robert, additional, Bogaard, Harm J., additional, Witzenrath, Martin, additional, Kuebler, Wolfgang M., additional, Szulcek, Robert, additional, and Simmons, Szandor, additional

Published
2023
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32. 3′-Deoxy-3′-[18F]Fluorothymidine Positron Emission Tomography Depicts Heterogeneous Proliferation Pathology in Idiopathic Pulmonary Arterial Hypertension Patient Lung: A Potential Biomarker for Pulmonary Arterial Hypertension

Author

Ashek, Ali, Spruijt, Onno A., Harms, Hendrik J., Lammertsma, Adriaan A., Cupitt, John, Dubois, Olivier, Wharton, John, Dabral, Swati, Pullamsetti, Soni Savai, Huisman, Marc C., Frings, Virginie, Boellaard, Ronald, de Man, Frances S., Botros, Lisa, Jansen, Samara, Vonk Noordegraaf, Anton, Wilkins, Martin R., Bogaard, Harm J., and Zhao, Lan

Published
2018
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33. Abstract 14753: Loss of Function ABCC8 Mutations Are Associated With Pulmonary Arterial Hypertension

Author

Bohnen, Michael S, Ma, Lijiang, Zhu, Na, Qi, Hongjian, McClenaghan, Conor, Gonzaga-Jauregui, Claudia, Dewey, Frederick E, Overton, John D, Reid, Jeffrey G, Shuldiner, Alan R, Baras, Aris, Sampson, Kevin J, Bleda, Marta, Hadinnapola, Charaka, Haimel, Matthias, Bogaard, Harm J, Church, Colin, Coghlan, Gerry, Corris, Paul A, Eyries, Mélanie, Gibbs, J. Simon R, Girerd, Barbara, Houweling, Arjan C, Humbert, Marc, Kiely, David G, Lawrie, Allan, MacKenzie Ross, Rob V, Martin, Jennifer M, Montani, David, Peacock, Andrew J, Pepke-Zaba, Joanna, Soubrier, Florent, Suntharalingam, Jay, Toshner, Mark, Treacy, Carmen M, Trembath, Richard C, Vonk Noordegraaf, Anton, Wharton, John, Wilkins, Martin R, Wort, Stephen J, Yates, Katherine, Gräf, Stefan, Morrell, Nicholas W, Krishnan, Usha, Rosenzweig, Erika B, Shen, Yufeng, Nichols, Colin G, Kass, Robert S, and Chung, Wendy K

Published
2017

38. Contributors

Author

Ahmed, Farah, Armstrong, Catherine, Bakalakos, Athanasios, Balasubramanian, Meena, Baritussio, Anna, Bhatia, Raghav T., Bogaard, Harm J., Bogaard, Harm Jan, Boomars, Karin A., Bueser, Teofila, Caforio, Alida LP., Carmo-Fonseca, M., Carvalho, Teresa, Celant, Lucas R., Chatrath, Nikhil, Cornel, Martina C., Dooijes, Dennis, du Toit, Clea, Elliott, Perry Mark, Furtado, Marta, Giordani, Andrea Silvio, Houweling, Arjan C., Iliceto, Sabino, Jansen, Samara M.A., Kassi, Maria, Koudstaal, Thomas, Kukavica, Deni, Kumar, Dhavendra, Lambiase, Pier D., Loeys, Bart L., Louca, Panayiotis, Lovering, Ruth C., Malfait, Fransiska, Marcolongo, Renzo, Markus, Hugh Stephen, Martins, Sandra, Menni, Cristina, Mercer, Catherine L., Monserrat, Lorenzo, Munroe, Patricia B., Nogal, Ana, Olczak, Kaya, Padmanabhan, Sandosh, Papadakis, Michael, Perkins, Jonathan A., Pilichou, Kalliopi, Priori, Silvia G., Ribeiro, Marta, Sharma, Sanjay, Tan, Rhea Yan Ying, Valdes, Ana M., van de Beek, Irma, van der Crabben, Saskia N., Van Gucht, Ilse, Verstraeten, Aline, Wilson, Dirk G., and Young, William J.

Published
2024
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39. Development of a 3-Dimensional Model to Study Right Heart Dysfunction in Pulmonary Arterial Hypertension: First Observations

Author

Llucià-Valldeperas, Aida, primary, Smal, Rowan, additional, Bekedam, Fjodor T., additional, Cé, Margaux, additional, Pan, Xiaoke, additional, Manz, Xue D., additional, Wijnker, Paul J. M., additional, Vonk-Noordegraaf, Anton, additional, Bogaard, Harm J., additional, Goumans, Marie-Jose, additional, and Man, Frances S. de, additional

Published
2021
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41. Abstract 10462: Increased Bone Morphogenetic Protein 10 Activity is Associated with Increased Right Atrial Wall Stress and Disease Severity in Pulmonary Hypertension

Author

Llucià-Valldeperas, Aida, primary, Van Wezenbeek, Jessie, additional, Groeneveldt, Joanne A, additional, Sanchez-Duffhues, Gonzalo, additional, Smal, Rowan, additional, Pan, Xiaoke, additional, vonk noordegraaf, anton, additional, Bogaard, Harm J, additional, Goumans, Marie Jose, additional, and De Man, Frances S, additional

Published
2021
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42. Abstract 9675: Right Ventricular and Right Atrial Function in Pulmonary Hypertension Secondary to Heart Failure With Preserved Ejection Fraction: A Comparison With Pulmonary Arterial Hypertension

Author

Van Wezenbeek, Jessie, primary, Kianzad, Azar, additional, Van De Bovenkamp, Arno, additional, Wessels, Jeroen, additional, Mouratoglou, Sophia-Anastasia, additional, Braams, Natalia, additional, Jansen, Samara, additional, Meulblok, Eva, additional, Meijboom, Lilian J, additional, Marcus, J. Tim T, additional, vonk noordegraaf, anton, additional, Goumans, Marie Jose, additional, Bogaard, Harm J, additional, Handoko, M L, additional, and De Man, Frances S, additional

Published
2021
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43. Abstract 14033: Inhibition of the Prolyl Isomerase Pin1 Improves Endothelial Function and Attenuates Vascular Remodelling in Pulmonary Hypertension by Inhibiting TGF-β Signalling

Author

Kurakula, Kondababu, primary, Hagdorn, Quint, additional, Van Der Feen, Diederik, additional, vonk noordegraaf, anton, additional, Dijke, Peter, additional, De Boer, Rudolf A, additional, Bogaard, Harm J, additional, Goumans, Marie Jose, additional, and Berger, Rolf M, additional

Published
2021
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46. Delayed Microvascular Shear Adaptation in Pulmonary Arterial Hypertension. Role of Platelet Endothelial Cell Adhesion Molecule-1 Cleavage

Author

Szulcek, Robert, Happé, Chris M., Rol, Nina, Fontijn, Ruud D., Dickhoff, Chris, Hartemink, Koen J., Grünberg, Katrien, Tu, Ly, Timens, Wim, Nossent, George D., Paul, Marinus A., Leyen, Thomas A., Horrevoets, Anton J., de Man, Frances S., Guignabert, Christophe, Yu, Paul B., Vonk-Noordegraaf, Anton, van Nieuw Amerongen, Geerten P., and Bogaard, Harm J.

Published
2016
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48. Rare variant analysis of 4241 pulmonary arterial hypertension cases from an international consortium implicates FBLN2, PDGFD, and rare de novo variants in PAH

Author

Zhu, Na, Swietlik, Emilia M., Welch, Carrie L., Pauciulo, Michael W., Hagen, Jacob J., Zhou, Xueya, Guo, Yicheng, Karten, Johannes, Pandya, Divya, Tilly, Tobias, Lutz, Katie A., Martin, Jennifer M., Treacy, Carmen M., Rosenzweig, Erika B., Krishnan, Usha, Coleman, Anna W., Gonzaga-Jauregui, Claudia, Lawrie, Allan, Trembath, Richard C., Wilkins, Martin R., Morrell, Nicholas W., Shen, Yufeng, Gräf, Stefan, Nichols, William C., Chung, Wendy K., Hirsch, Russel, White, R. James, Simon, Marc, Badesch, David, Rosenzweig, Erika, Burger, Charles, Chakinala, Murali, Thenappan, Thenappan, Elliott, Greg, Simms, Robert, Farber, Harrison, Frantz, Robert, Elwing, Jean, Hill, Nicholas, Ivy, Dunbar, Klinger, James, Nathan, Steven, Oudiz, Ronald, Robbins, Ivan, Schilz, Robert, Fortin, Terry, Wilt, Jeffrey, Yung, Delphine, Austin, Eric, Ahmad, Ferhaan, Bhatt, Nitin, Lahm, Tim, Frost, Adaani, Safdar, Zeenat, Rehman, Zia, Walter, Robert, Torres, Fernando, Bakshi, Sahil, Archer, Stephen, Argula, Rahul, Barnett, Christopher, Benza, Raymond, Desai, Ankit, Maddipati, Veeranna, Bogaard, Harm J., Church, Colin, Coghlin, Gerry, Condliffe, Robin, Eyries, Mélanie, Gall, Henning, Ghio, Stefano, Girerd, Barbara, Holden, Simon, Howard, Luke, Humbert, Marc, Kiely, David G., Kovacs, Gabor, Lordan, Jim, Machado, Rajiv D., MacKenzie Ross, Robert V., McCabe, Colm, Moledina, Shahin, Montani, David, Olschewski, Horst, Penkett, Christopher J., Pepke-Zaba, Joanna, Price, Laura, Rhodes, Christopher J., Seeger, Werner, Soubrier, Florent, Southgate, Laura, Suntharalingam, Jay, Swift, Andrew J., Toshner, Mark R., Noordegraaf, Anton Vonk, Wharton, John, Wild, Jim, Wort, Stephen John, and Apollo - University of Cambridge Repository

Subjects
Exome sequencing, Case-control association testing, Research, FOS: Biological sciences, Genetics, De novo variant analysis, Pulmonary arterial hypertension, Genome sequencing
Abstract

Background: Pulmonary arterial hypertension (PAH) is a lethal vasculopathy characterized by pathogenic remodeling of pulmonary arterioles leading to increased pulmonary pressures, right ventricular hypertrophy, and heart failure. PAH can be associated with other diseases (APAH: connective tissue diseases, congenital heart disease, and others) but often the etiology is idiopathic (IPAH). Mutations in bone morphogenetic protein receptor 2 (BMPR2) are the cause of most heritable cases but the vast majority of other cases are genetically undefined. Methods: To identify new risk genes, we utilized an international consortium of 4241 PAH cases with exome or genome sequencing data from the National Biological Sample and Data Repository for PAH, Columbia University Irving Medical Center, and the UK NIHR BioResource – Rare Diseases Study. The strength of this combined cohort is a doubling of the number of IPAH cases compared to either national cohort alone. We identified protein-coding variants and performed rare variant association analyses in unrelated participants of European ancestry, including 1647 IPAH cases and 18,819 controls. We also analyzed de novo variants in 124 pediatric trios enriched for IPAH and APAH-CHD. Results: Seven genes with rare deleterious variants were associated with IPAH with false discovery rate smaller than 0.1: three known genes (BMPR2, GDF2, and TBX4), two recently identified candidate genes (SOX17, KDR), and two new candidate genes (fibulin 2, FBLN2; platelet-derived growth factor D, PDGFD). The new genes were identified based solely on rare deleterious missense variants, a variant type that could not be adequately assessed in either cohort alone. The candidate genes exhibit expression patterns in lung and heart similar to that of known PAH risk genes, and most variants occur in conserved protein domains. For pediatric PAH, predicted deleterious de novo variants exhibited a significant burden compared to the background mutation rate (2.45×, p = 2.5e−5). At least eight novel pediatric candidate genes carrying de novo variants have plausible roles in lung/heart development. Conclusions: Rare variant analysis of a large international consortium identified two new candidate genes—FBLN2 and PDGFD. The new genes have known functions in vasculogenesis and remodeling. Trio analysis predicted that ~ 15% of pediatric IPAH may be explained by de novo variants.

Published
2021
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