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Pathophysiology of Primary Aldosteronism

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EC-Contrib. €

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Project "PAPA" data sheet

The following table provides information about the project.

Coordinator
LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN 

Organization address
address: GESCHWISTER SCHOLL PLATZ 1
city: MUENCHEN
postcode: 80539
website: www.uni-muenchen.de

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Germany [DE]
 Project website https://www.med.uni-muenchen.de/forschung/verbuende/ercgrants/papa/index.html
 Total cost 2˙496˙875 €
 EC max contribution 2˙496˙875 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-AdG
 Funding Scheme ERC-ADG
 Starting year 2017
 Duration (year-month-day) from 2017-01-01   to  2021-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN DE (MUENCHEN) coordinator 2˙496˙875.00

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 Project objective

Arterial hypertension is a major cardiovascular risk factor that affects between 10-40% of the population. Primary aldosteronism (PA) due to adrenal excess production of aldosterone is the most common secondary form of hypertension affecting 4-12% of hypertensives. Given the severe cardiovascular adverse effects of aldosterone excess early detection and individualized treatment of PA has important impact on clinical outcome and survival. However, the pathophysiology of PA is not well understood: While we recently identified specific genes underlying aldosterone producing adenoma, the most prevalent form of PA, bilateral adrenal hyperplasia, has remained enigmatic. It is the first hypothesis of this proposal that the pathophysiology of PA is a process based on two ‘hits’: agonistic angiotensin II type 1 receptor (AT1R) autoantibodies (proliferation, nodular hyperplasia) and somatic mutations (adenoma formation). It is the second hypothesis, that together, both factors induce not only aldosterone but also marked glucocorticoid excess. 1.) I will analyze prevalence and binding characteristics of AT1R autoantibodies as a pathophysiologic basis of PA. 2.) I will determine the effect of AT1R antibodies and genetic factors on cellular adrenal cortex models in vitro. 3.) I will extend these studies to specific in vivo genetic rodent models of PA. 4.) I will quantify aldosterone and glucocorticoid excess as disease effectors of AT1R autoantibodies and somatic mutations using liquid chromatography–mass spectrometry in PA. 5.) Using the generated data I will develop a pathophysiology-based concept of PA. This groundbreaking approach using innovative in vitro and in vivo models, state-of-the art genetic, immunologic and steroidobolomic techniques will uniquely open new avenues to the pathophysiologic understanding of PA. It will change our current understanding of PA, has high health impact and, thus, will pave the way to novel concepts of aldosterone excess and hypertension.

 Publications

year authors and title journal last update
List of publications.
2018 Tracy A. Williams, Jacopo Burrello, Leonardo A. Sechi, Carlos E. Fardella, Joanna Matrozova, Christian Adolf, René Baudrand, Stella Bernardi, Felix Beuschlein, Cristiana Catena, Michalis Doumas, Francesco Fallo, Gilberta Giacchetti, Daniel A. Heinrich, Gaëlle Saint-Hilary, Pieter M. Jansen, Andrzej Januszewicz, Tomaz Kocjan, Tetsuo Nishikawa, Marcus Quinkler, Fumitoshi Satoh, Hironobu Umakoshi, Jiří Widimský, Stefanie Hahner, Stella Douma, Michael Stowasser, Paolo Mulatero, Martin Reincke
Computed Tomography and Adrenal Venous Sampling in the Diagnosis of Unilateral Primary Aldosteronism
published pages: 641-649, ISSN: 0194-911X, DOI: 10.1161/HYPERTENSIONAHA.118.11382
Hypertension 72/3 2019-06-13
2018 Martin Reincke
Primary Aldosteronism and Cardiovascular Events
published pages: 413-414, ISSN: 0194-911X, DOI: 10.1161/HYPERTENSIONAHA.117.10405
Hypertension 71/3 2019-06-13
2017 Wiebke Arlt, Katharina Lang, Alice J. Sitch, Anna S. Dietz, Yara Rhayem, Irina Bancos, Annette Feuchtinger, Vasileios Chortis, Lorna C. Gilligan, Philippe Ludwig, Anna Riester, Evelyn Asbach, Beverly A. Hughes, Donna M. O’Neil, Martin Bidlingmaier, Jeremy W. Tomlinson, Zaki K. Hassan-Smith, D. Aled Rees, Christian Adolf, Stefanie Hahner, Marcus Quinkler, Tanja Dekkers, Jaap Deinum, Michael Biehl, Brian G. Keevil, Cedric H.L. Shackleton, Jonathan J. Deeks, Axel K. Walch, Felix Beuschlein, Martin Reincke
Steroid metabolome analysis reveals prevalent glucocorticoid excess in primary aldosteronism
published pages: , ISSN: 2379-3708, DOI: 10.1172/jci.insight.93136
JCI Insight 2/8 2019-06-13
2018 Britta Heinze, Carmina T. Fuss, Paolo Mulatero, Felix Beuschlein, Martin Reincke, Mona Mustafa, Andreas Schirbel, Timo Deutschbein, Tracy Ann Williams, Yara Rhayem, Marcus Quinkler, Nada Rayes, Silvia Monticone, Vanessa Wild, Celso E. Gomez-Sanchez, Anna-Carinna Reis, Stephan Petersenn, Hans-Juergen Wester, Saskia Kropf, Martin Fassnacht, Katharina Lang, Ken Herrmann, Andreas K. Buck, Christina Bluemel, Stefanie Hahner
Targeting CXCR4 (CXC Chemokine Receptor Type 4) for Molecular Imaging of Aldosterone-Producing Adenoma
published pages: 317-325, ISSN: 0194-911X, DOI: 10.1161/hypertensionaha.117.09975
Hypertension 71/2 2019-06-13
2017 Martin Reincke
Anxiety, Depression, and Impaired Quality of Life in Primary Aldosteronism: Why We Shouldn’t Ignore It!
published pages: 1-4, ISSN: 0021-972X, DOI: 10.1210/jc.2017-02141
The Journal of Clinical Endocrinology & Metabolism 103/1 2019-06-13
2017 Martin Reincke, Tracy Williams, Felix Beuschlein
Diagnosis and Treatment of Primary Aldosteronism in 2017: Did We Achieve Our Goals?
published pages: 905-907, ISSN: 0018-5043, DOI: 10.1055/s-0043-122145
Hormone and Metabolic Research 49/12 2019-06-13
2017 Celso Gomez-Sanchez, Maniselvan Kuppusamy, Martin Reincke, Tracy Williams
Disordered CYP11B2 Expression in Primary Aldosteronism
published pages: 957-962, ISSN: 0018-5043, DOI: 10.1055/s-0043-122238
Hormone and Metabolic Research 49/12 2019-06-13
2018 Tracy Ann Williams, Martin Reincke
MANAGEMENT OF ENDOCRINE DISEASE: Diagnosis and management of primary aldosteronism: the Endocrine Society guideline 2016 revisited
published pages: R19-R29, ISSN: 0804-4643, DOI: 10.1530/EJE-17-0990
European Journal of Endocrinology 179/1 2019-06-13
2017 Jacques Lenders, Graeme Eisenhofer, Martin Reincke
Subtyping of Patients with Primary Aldosteronism: An Update
published pages: 922-928, ISSN: 0018-5043, DOI: 10.1055/s-0043-122602
Hormone and Metabolic Research 49/12 2019-06-13
2017 Leticia Aragao-Santiago, Celso E Gomez-Sanchez, Paolo Mulatero, Ariadni Spyroglou, Martin Reincke, Tracy Ann Williams
Mouse Models of Primary Aldosteronism: From Physiology to Pathophysiology
published pages: 4129-4138, ISSN: 0013-7227, DOI: 10.1210/en.2017-00637
Endocrinology 158/12 2019-06-13
2017 Jacques W M Lenders, Tracy Ann Williams, Martin Reincke, Celso E Gomez-Sanchez
DIAGNOSIS OF ENDOCRINE DISEASE: 18-Oxocortisol and 18-hydroxycortisol: is there clinical utility of these steroids?
published pages: R1-R9, ISSN: 0804-4643, DOI: 10.1530/EJE-17-0563
European Journal of Endocrinology 178/1 2019-06-13
2017 Elke Tatjana Aristizabal Prada, Jacopo Burrello, Martin Reincke, Tracy Ann Williams
Old and New Concepts in the Molecular Pathogenesis of Primary Aldosteronism
published pages: 875-881, ISSN: 0194-911X, DOI: 10.1161/HYPERTENSIONAHA.117.10111
Hypertension 70/5 2019-06-13
2018 Lucie S. Meyer, Xiao Wang, Eva Sušnik, Jacopo Burrello, Alessio Burrello, Isabella Castellano, Graeme Eisenhofer, Francesco Fallo, Gregory A. Kline, Thomas Knösel, Tomaz Kocjan, Jacques W.M. Lenders, Paolo Mulatero, Mitsuhide Naruse, Tetsuo Nishikawa, Mirko Peitzsch, Lars C. Rump, Felix Beuschlein, Stefanie Hahner, Celso E. Gomez-Sanchez, Martin Reincke, Tracy Ann Williams
Immunohistopathology and Steroid Profiles Associated With Biochemical Outcomes After Adrenalectomy for Unilateral Primary Aldosteronism
published pages: 650-657, ISSN: 0194-911X, DOI: 10.1161/hypertensionaha.118.11465
Hypertension 72/3 2019-06-06
2019 Martin Reincke, Felix Beuschlein, Stefan Bornstein, Graeme Eisenhofer, Martin Fassnacht, Nicole Reisch, Tracy Williams
The Adrenal Gland: Central Relay in Health and Disease
published pages: 81-83, ISSN: 0947-7349, DOI: 10.1055/a-0752-4176
Experimental and Clinical Endocrinology & Diabetes 127/02/03 2019-05-22
2019 Yuhong Yang, Martin Reincke, Tracy Williams
Treatment of Unilateral PA by Adrenalectomy: Potential Reasons for Incomplete Biochemical Cure
published pages: 100-108, ISSN: 0947-7349, DOI: 10.1055/a-0662-6081
Experimental and Clinical Endocrinology & Diabetes 127/02/03 2019-05-22
2019 Jacopo Burrello, Alessio Burrello, Michael Stowasser, Tetsuo Nishikawa, Marcus Quinkler, Aleksander Prejbisz, Jacques W. M. Lenders, Fumitoshi Satoh, Paolo Mulatero, Martin Reincke, Tracy Ann Williams
The Primary Aldosteronism Surgical Outcome Score for the Prediction of Clinical Outcomes After Adrenalectomy for Unilateral Primary Aldosteronism
published pages: 1, ISSN: 0003-4932, DOI: 10.1097/sla.0000000000003200
Annals of Surgery 2019-05-22
2019 Yuhong Yang, Jacopo Burrello, Alessio Burrello, Graeme Eisenhofer, Mirko Peitzsch, Martina Tetti, Thomas Knösel, Felix Beuschlein, Jacques W.M. Lenders, Paolo Mulatero, Martin Reincke, Tracy Ann Williams
Classification of microadenomas in patients with primary aldosteronism by steroid profiling
published pages: , ISSN: 0960-0760, DOI: 10.1016/j.jsbmb.2019.01.008
The Journal of Steroid Biochemistry and Molecular Biology 2019-05-22
2017 Tracy A Williams, Jacques W M Lenders, Paolo Mulatero, Jacopo Burrello, Marietta Rottenkolber, Christian Adolf, Fumitoshi Satoh, Laurence Amar, Marcus Quinkler, Jaap Deinum, Felix Beuschlein, Kanako K Kitamoto, Uyen Pham, Ryo Morimoto, Hironobu Umakoshi, Aleksander Prejbisz, Tomaz Kocjan, Mitsuhide Naruse, Michael Stowasser, Tetsuo Nishikawa, William F Young, Celso E Gomez-Sanchez, John W Funder, Martin Reincke, Tracy Ann Williams, Celso E Gomez-Sanchez, John W Funder, Martin Reincke, Christian Adolf, Laurence Amar, Richard J Auchus, Detlef K Bartsch, Rene Baudrand, Felix Beuschlein, Peyman Björklund, Morris J Brown, Jacopo Burrello, Robert M Carey, Cristiana Catena, John M Connell, Jaap Deinum, Tanja Dekkers, Thomas J Fahey, Francesco Fallo, Carlos E. Fardella, Gilberta Giacchetti, Giuseppe Giraudo, Per Hellman, Andrzej Januszewicz, Kanako Kiriyama Kitamoto, Gregory A Kline, Tomaz Kocjan, Jacques W M Lenders, Franco Mantero, Barbra S Miller, Ryo Morimoto, Paolo Mulatero, Mitsuhide Naruse, Tetsuo Nishikawa, Uyen Pham, Pierre-François Plouin, Alexander Prejbisz, Marcus Quinkler, Marietta Rottenkolber, Christian L Rump, Fumitoshi Satoh, Leonardo A Sechi, Michael Stowasser, Hironobu Umakoshi, Franco Veglio, Jirí Widimský, Holger S Willenberg, William F Young
Outcomes after adrenalectomy for unilateral primary aldosteronism: an international consensus on outcome measures and analysis of remission rates in an international cohort
published pages: 689-699, ISSN: 2213-8587, DOI: 10.1016/s2213-8587(17)30135-3
The Lancet Diabetes & Endocrinology 5/9 2019-05-22
2019 Luis Perez-Rivas, Tracy Williams, Martin Reincke
Inherited Forms of Primary Hyperaldosteronism: New Genes, New Phenotypes and Proposition of A New Classification
published pages: 93-99, ISSN: 0947-7349, DOI: 10.1055/a-0713-0629
Experimental and Clinical Endocrinology & Diabetes 127/02/03 2019-05-22

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