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Start Over Author "Vonk-Noordegraaf A" Publisher american thoracic society
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1. Recurrent Pulmonary Veno-Occlusive Disease after Lung Transplantation.

Author

Nossent, Esther J., Nossent, Gregorius D., Meijboom, Lilian J., Verschuuren, Erik A. M., Gan, Christiaan T., Aman, Jurjan, Bogaard, Harm Jan, Radonic, Teodora, Dorfmüller, Peter, and Vonk Noordegraaf, Anton

Subjects
HEMATOPOIETIC stem cell transplantation, LUNG transplantation, POSITRON emission tomography, PULMONARY arterial hypertension, PULMONARY hypertension, HEPATIC veno-occlusive disease
Abstract

The article discusses a case of a 36-year-old female patient with idiopathic pulmonary veno-occlusive disease (PVOD) who experienced a recurrence of PVOD after undergoing bilateral lung transplantation. Despite initial successful recovery, the patient developed progressive dyspnea and pulmonary hypertension, leading to her unfortunate death due to right heart failure. The recurrence of PVOD in the donor lungs raises questions about potential extrapulmonary or systemic factors contributing to the disease's pathogenesis, emphasizing the need for further research in this area. [Extracted from the article]

Published
2024
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2. Mining the Plasma Proteome for Insights into the Molecular Pathology of Pulmonary Arterial Hypertension

Author

Lars Harbaum, Christopher J. Rhodes, John Wharton, Allan Lawrie, Jason H. Karnes, Ankit A. Desai, William C. Nichols, Marc Humbert, David Montani, Barbara Girerd, Olivier Sitbon, Mario Boehm, Tatyana Novoyatleva, Ralph T. Schermuly, H. Ardeschir Ghofrani, Mark Toshner, David G. Kiely, Luke S. Howard, Emilia M. Swietlik, Stefan Gräf, Maik Pietzner, Nicholas W. Morrell, Martin R. Wilkins, L Southgate, RD Machado, J Martin, WH Ouwehand, MW Pauciulo, A Arora, K Lutz, F Ahmad, SL Archer, R Argula, ED Austin, D Badesch, S Bakshi, C Barnett, R Benza, N Bhatt, CD Burger, M Chakinala, J Elwing, T Fortin, RP Frantz, A Frost, JGN Garcia, J Harley, H He, NS Hill, R Hirsch, D Ivy, J Klinger, T Lahm, K Marsolo, LJ Martin, SD Nathan, RJ Oudiz, Z Rehman, I Robbins, DM Roden, EB Rosenzweig, G Saydain, R Schilz, RW Simms, M Simon, H Tang, AY Tchourbanov, T Thenappan, F Torres, AK Walsworth, RE Walter, RJ White, J Wilt, D Yung, R Kittles, J Aman, J Knight, KB Hanscombe, H Gall, A Ulrich, HJ Bogaard, C Church, JG Coghlan, R Condliffe, PA Corris, C Danesino, CG Elliott, A Franke, S Ghio, JSR Gibbs, AC Houweling, G Kovacs, M Laudes, RV MacKenzie Ross, S Moledina, M Newnham, A Olschewski, H Olschewski, AJ Peacock, J Pepke-Zaba, L Scelsi, W Seeger, CM Shaffer, O Sitbon, J Suntharalingam, C Treacy, A Vonk Noordegraaf, Q Waisfisz, SJ Wort, RC Trembath, M Germain, I Cebola, J Ferrer, P Amouyel, S Debette, M Eyries, F Soubrier, DA Trégouët, Harbaum, Lars [0000-0002-9422-6195], Lawrie, Allan [0000-0003-4192-9505], Montani, David [0000-0002-9358-6922], Sitbon, Olivier [0000-0002-1942-1951], Gräf, Stefan [0000-0002-1315-8873], Wilkins, Martin R [0000-0003-3926-1171], Apollo - University of Cambridge Repository, British Heart Foundation, and The Academy of Medical Sciences

Subjects
Pulmonary and Respiratory Medicine, Pulmonary Arterial Hypertension, Proteome, case-control studies, Hypertension, Pulmonary, Respiratory System, Blood Proteins, Critical Care and Intensive Care Medicine, Mendelian randomization, Humans, Familial Primary Pulmonary Hypertension, Netrins, Pathology, Molecular, Mendelian randomisation, protein quantitative trait loci, Thrombospondins, genome, 11 Medical and Health Sciences
Abstract

Rationale: Pulmonary arterial hypertension (PAH) is characterized by structural remodeling of pulmonary arteries and arterioles. Underlying biological processes are likely reflected in a perturbation of circulating proteins. Objectives: To quantify and analyze the plasma proteome of patients with PAH using inherited genetic variation to inform on underlying molecular drivers. Methods: An aptamer-based assay was used to measure plasma proteins in 357 patients with idiopathic or heritable PAH, 103 healthy volunteers, and 23 relatives of patients with PAH. In discovery and replication subgroups, the plasma proteomes of PAH and healthy individuals were compared, and the relationship to transplantation-free survival in PAH was determined. To examine causal relationships to PAH, protein quantitative trait loci (pQTL) that influenced protein levels in the patient population were used as instruments for Mendelian randomization (MR) analysis. Measurements and Main Results: From 4,152 annotated plasma proteins, levels of 208 differed between patients with PAH and healthy subjects, and 49 predicted long-term survival. MR based on cis-pQTL located in proximity to the encoding gene for proteins that were prognostic and distinguished PAH from health estimated an adverse effect for higher levels of netrin-4 (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.16-2.08) and a protective effect for higher levels of thrombospondin-2 (OR, 0.83; 95% CI, 0.74-0.94) on PAH. Both proteins tracked the development of PAH in previously healthy relatives and changes in thrombospondin-2 associated with pulmonary arterial pressure at disease onset. Conclusions: Integrated analysis of the plasma proteome and genome implicates two secreted matrix-binding proteins, netrin-4 and thrombospondin-2, in the pathobiology of PAH.

Published
2022

3. Mining the Plasma Proteome for Insights into the Molecular Pathology of Pulmonary Arterial Hypertension

Author

Harbaum, Lars, primary, Rhodes, Christopher J., additional, Wharton, John, additional, Lawrie, Allan, additional, Karnes, Jason H., additional, Desai, Ankit A., additional, Nichols, William C., additional, Humbert, Marc, additional, Montani, David, additional, Girerd, Barbara, additional, Sitbon, Olivier, additional, Boehm, Mario, additional, Novoyatleva, Tatyana, additional, Schermuly, Ralph T., additional, Ghofrani, H. Ardeschir, additional, Toshner, Mark, additional, Kiely, David G., additional, Howard, Luke S., additional, Swietlik, Emilia M., additional, Gräf, Stefan, additional, Pietzner, Maik, additional, Morrell, Nicholas W., additional, Wilkins, Martin R., additional, Southgate, L, additional, Machado, RD, additional, Martin, J, additional, Ouwehand, WH, additional, Pauciulo, MW, additional, Arora, A, additional, Lutz, K, additional, Ahmad, F, additional, Archer, SL, additional, Argula, R, additional, Austin, ED, additional, Badesch, D, additional, Bakshi, S, additional, Barnett, C, additional, Benza, R, additional, Bhatt, N, additional, Burger, CD, additional, Chakinala, M, additional, Elwing, J, additional, Fortin, T, additional, Frantz, RP, additional, Frost, A, additional, Garcia, JGN, additional, Harley, J, additional, He, H, additional, Hill, NS, additional, Hirsch, R, additional, Ivy, D, additional, Klinger, J, additional, Lahm, T, additional, Marsolo, K, additional, Martin, LJ, additional, Nathan, SD, additional, Oudiz, RJ, additional, Rehman, Z, additional, Robbins, I, additional, Roden, DM, additional, Rosenzweig, EB, additional, Saydain, G, additional, Schilz, R, additional, Simms, RW, additional, Simon, M, additional, Tang, H, additional, Tchourbanov, AY, additional, Thenappan, T, additional, Torres, F, additional, Walsworth, AK, additional, Walter, RE, additional, White, RJ, additional, Wilt, J, additional, Yung, D, additional, Kittles, R, additional, Aman, J, additional, Knight, J, additional, Hanscombe, KB, additional, Gall, H, additional, Ulrich, A, additional, Bogaard, HJ, additional, Church, C, additional, Coghlan, JG, additional, Condliffe, R, additional, Corris, PA, additional, Danesino, C, additional, Elliott, CG, additional, Franke, A, additional, Ghio, S, additional, Gibbs, JSR, additional, Houweling, AC, additional, Kovacs, G, additional, Laudes, M, additional, MacKenzie Ross, RV, additional, Moledina, S, additional, Newnham, M, additional, Olschewski, A, additional, Olschewski, H, additional, Peacock, AJ, additional, Pepke-Zaba, J, additional, Scelsi, L, additional, Seeger, W, additional, Shaffer, CM, additional, Sitbon, O, additional, Suntharalingam, J, additional, Treacy, C, additional, Vonk Noordegraaf, A, additional, Waisfisz, Q, additional, Wort, SJ, additional, Trembath, RC, additional, Germain, M, additional, Cebola, I, additional, Ferrer, J, additional, Amouyel, P, additional, Debette, S, additional, Eyries, M, additional, Soubrier, F, additional, and Trégouët, DA, additional

Published
2022
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6. A New Clinical Phenotype with Non-Plexiform Vasculopathy and Distinctive Microvessel Remodeling Among Idiopathic Pulmonary Arterial Hypertension Patients

Author

Nossent, E.J., primary, Smits, J., additional, Seegers, C., additional, Meijboom, L., additional, Boonstra, A., additional, Tran-Lundmark, K., additional, Aman, J., additional, De Man, F., additional, Bogaard, H.J., additional, Radonic, T., additional, Dorfmüller, P., additional, and Vonk Noordegraaf, A., additional

Published
2022
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9. Right Ventricular Load and Function in Chronic Thromboembolic Pulmonary Hypertension: Differences between Proximal and Distal Chronic Thromboembolic Pulmonary Hypertension

Author

Esther J. Nossent, Anna E. Huis In ‘t Veld, Anton Vonk Noordegraaf, Harm-Jan Bogaard, Cathelijne E. E. van der Bruggen, Berend E. Westerhof, Dieuwertje Ruigrok, J. Tim Marcus, Petr Symersky, Lilian J. Meijboom, Academic Medical Center, Radiology and nuclear medicine, Pulmonary medicine, ACS - Pulmonary hypertension & thrombosis, APH - Quality of Care, Cardio-thoracic surgery, ACS - Atherosclerosis & ischemic syndromes, and ACS - Heart failure & arrhythmias

Subjects
Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Computed Tomography Angiography, business.industry, Hypertension, Pulmonary, Ventricular Dysfunction, Right, Middle Aged, Pulmonary Artery, Critical Care and Intensive Care Medicine, Magnetic Resonance Imaging, Internal medicine, Chronic Disease, medicine, Cardiology, Humans, Female, Chronic thromboembolic pulmonary hypertension, Pulmonary Embolism, business, Aged, Retrospective Studies
Published
2019
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10. Increased BMP10 Levels Are Associated with Pulmonary Hypertension

Author

Llucia-Valldeperas, A., primary, van Wezenbeek, J., additional, Groeneveldt, J.A., additional, Sanchez-Duffhues, G., additional, Smal, R., additional, Pan, X., additional, Vonk Noordegraaf, A., additional, Bogaard, H.J., additional, Goumans, M.-J., additional, and De Man, F.S., additional

Published
2021
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11. Increased MAO-A Activity Promotes Progression of Pulmonary Arterial Hypertension

Author

Sun, Xiao-Qing, primary, Peters, Eva L., additional, Schalij, Ingrid, additional, Axelsen, Julie Birkmose, additional, Andersen, Stine, additional, Kurakula, Kondababu, additional, Gomez-Puerto, Maria Catalina, additional, Szulcek, Robert, additional, Pan, Xiaoke, additional, da Silva Goncalves Bos, Denielli, additional, Schiepers, Roy E. J., additional, Andersen, Asger, additional, Goumans, Marie-José, additional, Vonk Noordegraaf, Anton, additional, van der Laarse, Willem J., additional, de Man, Frances S., additional, and Bogaard, Harm Jan, additional

Published
2021
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12. The Effects of Mercaptopurine on Pulmonary Vascular Resistance and BMPR2 Expression in Pulmonary Arterial Hypertension

Author

Botros, Liza, primary, Szulcek, Robert, additional, Jansen, Samara M. A., additional, Kurakula, Kondababu, additional, Goumans, Marie-José T. H., additional, van Kuilenburg, André B. P., additional, Vonk Noordegraaf, Anton, additional, de Man, Frances S., additional, Aman, Jurjan, additional, and Bogaard, Harm Jan, additional

Published
2020
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13. Comparison of Human and Experimental Pulmonary Veno-Occlusive Disease

Author

Manaud, Grégoire, primary, Nossent, Esther J., additional, Lambert, Mélanie, additional, Ghigna, Maria-Rosa, additional, Boët, Angèle, additional, Vinhas, Maria-Candida, additional, Ranchoux, Benoit, additional, Dumas, Sébastien J., additional, Courboulin, Audrey, additional, Girerd, Barbara, additional, Soubrier, Florent, additional, Bignard, Juliette, additional, Claude, Olivier, additional, Lecerf, Florence, additional, Hautefort, Aurélie, additional, Florio, Monica, additional, Sun, Banghua, additional, Nadaud, Sophie, additional, Verleden, Stijn E., additional, Remy, Séverine, additional, Anegon, Ignacio, additional, Bogaard, Harm Jan, additional, Mercier, Olaf, additional, Fadel, Elie, additional, Simonneau, Gérald, additional, Vonk Noordegraaf, Anton, additional, Grünberg, Katrien, additional, Humbert, Marc, additional, Montani, David, additional, Dorfmüller, Peter, additional, Antigny, Fabrice, additional, and Perros, Frédéric, additional

Published
2020
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14. Anti-Proliferative Therapy with 6-Mercaptopurine Improves Hemodynamics and BMPR2 Expression in Pulmonary Arterial Hypertension

Author

Botros, L., primary, Szulcek, R., additional, Jansen, S., additional, Smits, J., additional, Phelp, P., additional, Kurakula, K., additional, Goumans, M.-J., additional, Nossent, E.J., additional, Boonstra, A., additional, Vonk Noordegraaf, A., additional, De Man, F., additional, Aman, J., additional, and Bogaard, H.J., additional

Published
2020
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17. The Sex-Age Interactions in Pulmonary Arterial Hypertension

Author

A. Vonk Noordegraaf, J. A. Groeneveldt, P. Trip, C. E. E. van der Bruggen, F.S. de Man, Berend E. Westerhof, Pulmonary medicine, ACS - Pulmonary hypertension & thrombosis, APH - Quality of Care, ACS - Atherosclerosis & ischemic syndromes, and ACS - Heart failure & arrhythmias

Subjects
medicine.medical_specialty, business.industry, Internal medicine, medicine, Cardiology, business
Published
2019
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20. Pulmonary Hypertension in a Nonreferral Setting in the Netherlands: Incidence and Patient Characteristics in the Optics Registry

Author

Jansen, S., primary, Huis in 't Veld, A.E., additional, Tolen, P.C.G., additional, Jacobs, W., additional, Grotjohan, H.P., additional, Waskowsky, W., additional, van der Maten, J., additional, van der Weerdt, A., additional, Hoekstra, R., additional, Overbeek, M., additional, Mollema, S., additional, Hassan el Bouazzaoui, L.H., additional, Vriend, J., additional, Roorda, M., additional, de Nooijer, R., additional, van der Lee, I., additional, Voogel, A.J., additional, Peels, C., additional, Aerts, J.G., additional, Van De Ven, M., additional, De Man, F., additional, Vonk Noordegraaf, A., additional, and Bogaard, H.J., additional

Published
2019
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21. Right Ventricular Load and Function in Chronic Thromboembolic Pulmonary Hypertension: Differences between Proximal and Distal Chronic Thromboembolic Pulmonary Hypertension

Author

Ruigrok, Dieuwertje, primary, Meijboom, Lilian J., additional, Westerhof, Berend E., additional, in ’t Veld, Anna Huis, additional, van der Bruggen, Cathelijne E. E., additional, Marcus, J. Tim, additional, Nossent, Esther J., additional, Vonk Noordegraaf, Anton, additional, Symersky, Petr, additional, and Bogaard, Harm-Jan, additional

Published
2019
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22. The Effects of Exercise on Right Ventricular Contractility and Right Ventricular–Arterial Coupling in Pulmonary Hypertension

Author

Herman Groepenhoff, Harm-Jan Bogaard, Frances S. de Man, Frank P. T. Oosterveer, Onno A. Spruijt, Nico Westerhof, Anton Vonk-Noordegraaf, Pulmonary medicine, Physiology, and ICaR - Heartfailure and pulmonary arterial hypertension

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, Pulmonary Circulation, medicine.medical_specialty, Hypertension, Pulmonary, Ventricular Dysfunction, Right, Exercise intolerance, Critical Care and Intensive Care Medicine, Afterload, Internal medicine, medicine.artery, medicine, Humans, In patient, Prospective Studies, Exercise, Ventricular arterial coupling, Ventricular contractility, business.industry, Middle Aged, Control subjects, medicine.disease, Myocardial Contraction, Pulmonary hypertension, Anesthesia, Pulmonary artery, Ventricular Function, Right, Cardiology, Female, medicine.symptom, business
Abstract

Exercise tolerance is decreased in patients with pulmonary hypertension (PH). It is unknown whether exercise intolerance in PH coincides with an impaired rest-to-exercise response in right ventricular (RV) contractility.To investigate in patients with PH the RV exertional contractile reserve, defined as the rest-to-exercise response in end-systolic elastance (ΔEes), and the effects of exercise on the matching of Ees and RV afterload (Ea) (i.e., RV-arterial coupling; Ees/Ea). In addition, we compared ΔEes with a recently proposed surrogate, the rest-to-exercise change in pulmonary artery pressure (ΔPAP).We prospectively included 17 patients with precapillary PH and 7 control subjects without PH who performed a submaximal invasive cardiopulmonary exercise test between January 2013 and July 2014. Ees and Ees/Ea were assessed using single-beat pressure-volume loop analysis.Exercise data in 16 patients with PH and 5 control subjects were of sufficient quality for analysis. Ees significantly increased from rest to exercise in control subjects but not in patients with PH. Ea significantly increased in both groups. As a result, exercise led to a decrease in Ees/Ea in patients with PH, whereas Ees/Ea was unaffected in control subjects (Pinteraction = 0.009). In patients with PH, ΔPAP was not related to ΔEes but significantly correlated to the rest-to-exercise change in heart rate.In contrast to control subjects, patients with PH were unable to increase Ees during submaximal exercise. Failure to compensate for the further increase in Ea during exercise led to deterioration in Ees/Ea. Furthermore, ΔPAP did not reflect ΔEes but rather the change in heart rate.

Published
2015
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23. Increased MAO-A Activity Promotes Progression of Pulmonary Arterial Hypertension.

Author

Xiao-Qing Sun, Peters, Eva L., Schalij, Ingrid, Birkmose Axelsen, Julie, Andersen, Stine, Kurakula, Kondababu, Gomez-Puerto, Maria Catalina, Szulcek, Robert, Xiaoke Pan, da Silva Goncalves Bos, Denielli, Schiepers, Roy E. J., Andersen, Asger, Goumans, Marie-José, Vonk Noordegraaf, Anton, van der Laarse, Willem J., de Man, Frances S., and Bogaard, Harm Jan

Subjects
MONOAMINE oxidase, HYPEREMIA, MITOCHONDRIAL membranes, HYPOXEMIA, OXIDATIVE stress
Abstract

Monoamine oxidases (MAOs), a class of enzymes bound to the outer mitochondrial membrane, are important sources of reactive oxygen species. Increased MAO-A activity in endothelial cells and cardiomyocytes contributes to vascular dysfunction and progression of left heart failure. We hypothesized that inhibition of MAO-A can be used to treat pulmonary arterial hypertension (PAH) and right ventricular (RV) failure. MAO-A levels in lung and RV samples from patients withPAHwere compared with levels in samples from donors without PAH. Experimental PAH was induced in male Sprague- Dawley rats by using Sugen 5416 and hypoxia (SuHx), and RV failure was induced in male Wistar rats by using pulmonary trunk banding (PTB). Animals were randomized to receive either saline or the MAO-A inhibitor clorgyline at 10 mg/kg. Echocardiography and RV catheterization were performed, and heart and lung tissues were collected for further analysis. We found increased MAO-A expression in the pulmonary vasculature of patients with PAHand in experimental experimental PAH induced by SuHx. Cardiac MAO-A expression and activity was increased in SuHx- and PTB-induced RV failure. Clorgyline treatment reduced RV afterload and pulmonary vascular remodeling in SuHx rats through reduced pulmonary vascular proliferation and oxidative stress. Moreover, clorgyline improved RV stiffness and relaxation and reversed RV hypertrophy in SuHx rats. In PTB rats, clorgyline had no direct clorgyline had no direct effect on the right ventricle effect. Our study reveals the role of MAO-A in the progression of PAH. Collectively, these findings indicated that MAO-A may be involved in pulmonary vascular remodeling and consecutive RV failure. [ABSTRACT FROM AUTHOR]

Published
2021
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24. Assessment of Right Ventricular Function in the Research Setting: Knowledge Gaps and Pathways Forward. An Official American Thoracic Society Research Statement

Author

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

Published
2018
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25. Delayed Microvascular Shear Adaptation in Pulmonary Arterial Hypertension. Role of Platelet Endothelial Cell Adhesion Molecule-1 Cleavage

Author

Chris Happé, Marinus A. Paul, Geerten P. van Nieuw Amerongen, Anton Vonk-Noordegraaf, Harm Jan Bogaard, Katrien Grünberg, Koen J. Hartemink, Christophe Guignabert, Thomas A. Leyen, Robert Szulcek, Frances S. de Man, Ruud D. Fontijn, Chris Dickhoff, Anton J.G. Horrevoets, G.D. Nossent, Wim Timens, Nina Rol, Paul B. Yu, Ly Tu, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Groningen Research Institute for Asthma and COPD (GRIAC), Pulmonary medicine, ICaR - Heartfailure and pulmonary arterial hypertension, ICaR - Ischemia and repair, Molecular cell biology and Immunology, Cardio-thoracic surgery, Surgery, Pathology, Physiology, and Amsterdam institute for Infection and Immunity

Subjects
Male, 0301 basic medicine, Pathology, medicine.medical_treatment, PATHOGENESIS, Fluorescent Antibody Technique, Hemodynamics, Critical Care and Intensive Care Medicine, Polymerase Chain Reaction, pulmonary arterial hypertension, RAT MODEL, molecular biology, Familial Primary Pulmonary Hypertension, Endothelial dysfunction, Child, Cells, Cultured, PROLIFERATION, Middle Aged, INTEGRITY, Platelet Endothelial Cell Adhesion Molecule-1, Endothelial stem cell, HEMODYNAMICS, Hypertension, endothelial cell, cardiovascular system, Female, Original Article, medicine.symptom, Adult, Pulmonary and Respiratory Medicine, GROWTH-FACTOR, medicine.medical_specialty, PECAM-1, Hypertension, Pulmonary, Blotting, Western, microcirculation, Inflammation, Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9], Pulmonary Artery, Vascular Remodeling, shear stress, Microcirculation, Young Adult, 03 medical and health sciences, RECEPTOR-2, INFLAMMATION, medicine.artery, medicine, Animals, Humans, CASPASE INHIBITOR, business.industry, Growth factor, medicine.disease, Pulmonary hypertension, Rats, Disease Models, Animal, 030104 developmental biology, Microvessels, Pulmonary artery, Stress, Mechanical, business
Abstract

Item does not contain fulltext RATIONALE: Altered pulmonary hemodynamics and fluid flow-induced high shear stress (HSS) are characteristic hallmarks in the pathogenesis of pulmonary arterial hypertension (PAH). However, the contribution of HSS to cellular and vascular alterations in PAH is unclear. OBJECTIVES: We hypothesize that failing shear adaptation is an essential part of the endothelial dysfunction in all forms of PAH and tested whether microvascular endothelial cells (MVECs) or pulmonary arterial endothelial cells (PAECs) from lungs of patients with PAH adapt to HSS and if the shear defect partakes in vascular remodeling in vivo. METHODS: PAH MVEC (n = 7) and PAH PAEC (n = 3) morphology, function, protein, and gene expressions were compared with control MVEC (n = 8) under static culture conditions and after 24, 72, and 120 hours of HSS. MEASUREMENTS AND MAIN RESULTS: PAH MVEC showed a significantly delayed morphological shear adaptation (P = 0.03) and evidence of cell injury at sites of nonuniform shear profiles that are critical loci for vascular remodeling in PAH. In clear contrast, PAEC isolated from the same PAH lungs showed no impairments. PAH MVEC gene expression and transcriptional shear activation were not altered but showed significant decreased protein levels (P = 0.02) and disturbed interendothelial localization of the shear sensor platelet endothelial cell adhesion molecule-1 (PECAM-1). The decreased PECAM-1 levels were caused by caspase-mediated cytoplasmic cleavage but not increased cell apoptosis. Caspase blockade stabilized PECAM-1 levels, restored endothelial shear responsiveness in vitro, and attenuated occlusive vascular remodeling in chronically hypoxic Sugen5416-treated rats modeling severe PAH. CONCLUSIONS: Delayed shear adaptation, which promotes shear-induced endothelial injury, is a newly identified dysfunction specific to the microvascular endothelium in PAH. The shear response is normalized on stabilization of PECAM-1, which reverses intimal remodeling in vivo.

Published
2016
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26. Right Ventricular Oscillatory Power Is a Constant Fraction of Total Power Irrespective of Pulmonary Artery Pressure

Author

Anton Vonk-Noordegraaf, Nabil Saouti, Anco Boonstra, Nico Westerhof, J. Tim Marcus, Frank Helderman, Pieter E. Postmus, Pulmonary medicine, Physiology, Physics and medical technology, and ICaR - Heartfailure and pulmonary arterial hypertension

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, Heart Ventricles, Hypertension, Pulmonary, Hemodynamics, Blood Pressure, Pulmonary Artery, Critical Care and Intensive Care Medicine, Pulmonary heart disease, medicine.artery, medicine, Humans, Pulmonary Wedge Pressure, Pulmonary wedge pressure, business.industry, Blood flow, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Pulmonary hypertension, medicine.anatomical_structure, Blood pressure, Ventricle, Case-Control Studies, Anesthesia, Pulmonary artery, Ventricular Function, Right, Female, business, Blood Flow Velocity
Abstract

Pulmonary hypertension (PH) is characterized by increased arterial load requiring more right ventricular (RV) hydraulic power to sustain adequate forward blood flow. Power can be separated into a mean and oscillatory part. The former is associated with mean and the latter with pulsatile blood flow and pressure. Because mean power provides for net blood flow, the ratio of oscillatory to total power (oscillatory power fraction) preferably should be small. It is unknown whether this is the case in pulmonary arterial hypertension (PAH).To derive components of power generated by the right ventricle in PAH.Thirty-five patients with idiopathic PAH (IPAH) and 14 subjects without PH were included. The patients were divided in two groups, "moderate" and "high," based on pulmonary artery (PA) pressure. PA pressures were obtained by right heart catheterization and PA flows by magnetic resonance imaging. Total hydraulic power (Power(total)) was calculated as the integral product of pressure and flow. Mean hydraulic power (Power(mean)) was calculated as mean pulmonary artery pressure times mean flow. Their difference is oscillatory power (Power(oscill)). Total hydraulic power in subjects without PH compared with moderate and high IPAH was 0.29 ± 0.10 W (n = 14), 0.52 ± 0.14 W (n = 17), and 0.73 ± 0.24 W (n = 18), respectively. The oscillatory power fraction is approximately 23% and not different between groups.In this study, oscillatory power fraction is constant at 23% in non-PH and IPAH, implying that a considerable amount of power is not used for forward flow, making the RV less efficient with respect to its arterial load. Our findings emphasize the need to develop new therapy strategies to optimize RV power output in PAH.

Published
2010
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27. Delayed Microvascular Shear Adaptation in Pulmonary Arterial Hypertension. Role of Platelet Endothelial Cell Adhesion Molecule-1 Cleavage

Author

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

Published
2016
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28. Right Ventricular Pressure Curves Are Essential In The Assessment Of Right Ventricular End-Systolic Elastance In Patients With Pulmonary Hypertension

Author

Harm Jan Bogaard, Anton Vonk-Noordegraaf, Mariëlle C. van de Veerdonk, J.T. Marcus, Pia Trip, Frances S. de Man, Nico Westerhof, and Taco Kind

Subjects
medicine.medical_specialty, End systolic elastance, business.industry, Internal medicine, Cardiology, Ventricular pressure, Medicine, In patient, business, medicine.disease, Pulmonary hypertension
Published
2012
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29. Myocardial Glucose Uptake In Pulmonary Arterial Hypertension: The Role Of Ventricular Mass And The Interventricular Septum

Author

J.T. Marcus, W. J. Van Der Laarse, Pieter G. Raijmakers, P E Postmus, Anton Vonk-Noordegraaf, Yeun Ying Wong, Mark Lubberink, F.S. de Man, Adriaan Lammertsma, Gerrina Ruiter, Anco Boonstra, and Nico Westerhof

Subjects
medicine.medical_specialty, medicine.anatomical_structure, business.industry, Internal medicine, Glucose uptake, medicine, Cardiology, Interventricular septum, Ventricular mass, business
Published
2012
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30. Imatinib: A Novel Candidate For Treatment Of Permeability Edema

Author

Jurjan Aman, Victor W.M. van Hinsbergh, Anton Vonk Noordegraaf, A. B. J. Groeneveld, Steven M. Vogel, Jan van Bezu, and Geerten P. van Nieuw Amerongen

Subjects
Permeability (earth sciences), business.industry, Edema, Medicine, Imatinib, Pharmacology, medicine.symptom, business, medicine.drug
Published
2012
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31. The Therapeutic Potential Of The Renin-Angiotensin-Aldosteron System In Idiopathic Pulmonary Arterial Hypertension

Author

P E Postmus, Gérald Simonneau, Silvia Rain, Christophe Guignabert, Frances S. de Man, Elie Fadel, Jolanda van der Velden, Saadia Eddahibi, Anton Vonk-Noordegraaf, Marc Humbert, Ingrid Schalij, Gerrina Ruiter, M. L. Handoko, Ly Tu, and Charlene Francois

Subjects
medicine.medical_specialty, business.industry, Internal medicine, Renin–angiotensin system, Idiopathic Pulmonary Arterial Hypertension, Cardiology, Medicine, business
Published
2012
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36. Proof-Of-Concept Study To Investigate The Efficacy, Hemodynamics And Tolerability Of Terguride Vs. Placebo In Subjects With Pulmonary Arterial Hypertension: Results Of A Double Blind, Randomised, Prospective Phase IIa Study

Author

Rudolf Reiter, Christian Opitz, Anton Vonk-Noordegraaf, Adam Torbicki, Ekkehard Gruenig, Claus Neurohr, Arthur Filusch, Christian M. Kaehler, Stephan Rosenkranz, Hikmet Al-Hiti, Marius M. Hoeper, Hossein Ardeschir Ghofrani, Pavel Jansa, Rudolf Speich, Juergen Behr, Heinrike Wilkens, Horst Olschewski, Michael Halank, and Ralf Ewert

Subjects
Double blind, Tolerability, business.industry, Anesthesia, Medicine, Hemodynamics, business, Placebo, Terguride, medicine.drug
Published
2012
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39. Is A Reduced Right Ventricular Function Associated With An Increased Acetate Metabolism Of The Right Ventricular Myocardium Measured With 11C Acetate PET-Scan?

Author

Harm Jan Bogaard, Anton Vonk-Noordegraaf, Hans Harms, Frances S. de Man, Karin de Boer, Jasmijn van Campen, Yeun Ying Wong, and Mariëlle C. van de Veerdonk

Subjects
medicine.medical_specialty, 11c acetate, Ventricular function, business.industry, Internal medicine, Cardiology, Medicine, business, Right ventricular myocardium, Acetate metabolism
Published
2012
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40. Diastolic Dysfunction In Idiopathic Pulmonary Arterial Hypertension

Author

Jolanda van der Velden, Anton Vonk-Noordegraaf, Nico Westerhof, Taco Kind, M. Louis Handoko, Frances S. de Man, Bart Boerrighter, and Silvia Rain

Subjects
medicine.medical_specialty, Blood pressure, business.industry, Internal medicine, Idiopathic Pulmonary Arterial Hypertension, Cardiology, Diastole, Medicine, business
Published
2011
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41. Underfilling Of The Right Atrium Is An Important Mechanism Of The Hemodynamic Impairment In Chronic Obstructive Pulmonary Disease

Author

Anton Vonk-Noordegraaf, Harm Jan Bogaard, Frank P. T. Oosterveer, Herman Groepenhoff, Nico Westerhof, Frank Helderman, and Bart Boerrigter

Subjects
medicine.medical_specialty, medicine.anatomical_structure, business.industry, Mechanism (biology), Internal medicine, Cardiology, Medicine, Right atrium, Pulmonary disease, Hemodynamics, business
Published
2011
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42. Right Ventricular Myoglobin Decrease In Human Pulmonary Hypertension

Author

Frances S. de Man, Yeun Ying Wong, Gerrina Ruiter, Willem J. van der Laarse, Hans W.M. Niessen, Pieter E. Postmus, Anton Vonk-Noordegraaf, and Nico Westerhof

Subjects
chemistry.chemical_compound, medicine.medical_specialty, Myoglobin, chemistry, business.industry, Internal medicine, Cardiology, Medicine, business, medicine.disease, Pulmonary hypertension
Published
2011
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43. Right Ventricular Filling Impairment During Exercise In COPD

Author

Harm Jan Bogaard, Anton Vonk-Noordegraaf, Tim Marcus, Nico Westerhof, Pia Trip, Bart Boerrigter, and Anco Boonstra

Subjects
medicine.medical_specialty, COPD, business.industry, Internal medicine, medicine, Cardiology, medicine.disease, business, Right ventricular filling
Published
2011
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46. Heart Rate And Mean Pulmonary Artery Pressure Relate With Myocardial Oxygen Consumption Of The Hypertrophied Right Ventricle In Pulmonary Hypertensive Patients

Author

Yeun Ying Wong, Anton Vonk-Noordegraaf, Gerrina Ruiter, W. J. Van Der Laarse, Nico Westerhof, Mark Lubberink, P.G.H.M. Raijmakers, and Paul Knaapen

Subjects
medicine.medical_specialty, medicine.anatomical_structure, Myocardial oxygen consumption, Ventricle, business.industry, Internal medicine, medicine.artery, Pulmonary artery, Heart rate, medicine, Cardiology, business, Pulmonary wedge pressure
Published
2011
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48. 'Danger Of Spirometry'

Author

Harm Jan Bogaard, Bart Boerrigter, and Anton Vonk-Noordegraaf

Subjects
Spirometry, medicine.medical_specialty, medicine.diagnostic_test, business.industry, Physical therapy, Medicine, business
Published
2011
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49. Chronic Treatment With Low-Dose Bisoprolol Improves Survival And Cardiac Function In Experimental Pulmonary Arterial Hypertension

Author

Nico Westerhof, Jolanda van der Velden, Frances S. de Man, M. L. Handoko, Anton Vonk-Noordegraaf, Ingrid Schalij, Walter Paulus, and Joris J.M. van Ballegoij

Subjects
Cardiac function curve, medicine.medical_specialty, business.industry, Low dose, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Bisoprolol, Internal medicine, Cardiology, Medicine, 030212 general & internal medicine, business, medicine.drug
Published
2010
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50. Diaphragm Dysfunction In Experimental Pulmonary Arterial Hypertension

Author

Frances S. de Man, Hans W.M. Niessen, Nico Westerhof, Pieter E. Postmus, Anton Vonk-Noordegraaf, Ger J.M. Stienen, Coen A.C. Ottenheijm, M. L. Handoko, Hieronymus W. H. van Hees, Ingrid Schalij, and Willem J. van der Laarse

Subjects
medicine.medical_specialty, business.industry, Internal medicine, medicine, Cardiology, business, Diaphragm (structural system)
Published
2010
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