Cel 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. Dziedzina nauki medical and health sciencesclinical medicinesurgerymedical and health sciencesbasic medicinephysiologypathophysiologynatural sciencesbiological sciencesgeneticsmutationmedical and health sciencesclinical medicinecardiologycardiovascular diseasesmedical and health sciencesbasic medicineneurologystroke Słowa kluczowe endocrine hypertension primary aldosteronism cortisol aldosterone Program(-y) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Temat(-y) ERC-ADG-2015 - ERC Advanced Grant Zaproszenie do składania wniosków ERC-2015-AdG Zobacz inne projekty w ramach tego zaproszenia System finansowania ERC-ADG - Advanced Grant Instytucja przyjmująca LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN Wkład UE netto € 2 496 875,00 Adres GESCHWISTER SCHOLL PLATZ 1 80539 Muenchen Niemcy Zobacz na mapie Region Bayern Oberbayern München, Kreisfreie Stadt Rodzaj działalności Higher or Secondary Education Establishments Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity € 2 496 875,00 Beneficjenci (1) Sortuj alfabetycznie Sortuj według wkładu UE netto Rozwiń wszystko Zwiń wszystko LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN Niemcy Wkład UE netto € 2 496 875,00 Adres GESCHWISTER SCHOLL PLATZ 1 80539 Muenchen Zobacz na mapie Region Bayern Oberbayern München, Kreisfreie Stadt Rodzaj działalności Higher or Secondary Education Establishments Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity € 2 496 875,00
