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Mineralocorticoid receptor: pathophysiology and therapeutic innovations

The aim of our current studies is to improve the understanding of the pathophysiological roles and signaling pathways whereby the hormone aldosterone promotes pathologies in various organs including the kidney and the cardiovascular system. Our work combines cellular and molecular approaches, animal physiology, pharmacological studies and has implications in human diseases. Our interest includes translational research aimed to identify and validate biomarkers of Mineralocorticoid Receptor activation in cardiovascular and kidney diseases and novel therapeutic use of MR antagonists.


Our work lead to:
1) Analysis of the pathophysiological role of the mineralocorticoid receptor in the heart. Characterization of mineralocorticoid/angiotensin II functional interactions. Identification of novel mineralocorticoid target genes in the heart (3 papers, 1 patent).

2) Identification of a novel target (Neutrophil Gelatinase-Associated Lipocalin, NGAL) of the mineralocorticoid receptor in the cardiovascular system which is proposed as a theranostic biomarker of mineralocorticoid receptor activation (allowing patient stratification and therapeutic decision) as well as an actor in extracellular matrix remodeling in the cardiovascular system (potential novel therapeutic target) (3 patents, 1 paper in 2012, 2 industrial partnership). Translational research is ongoing to validate NGAL as a biomarker in heart failure associated or not to metabolic syndrome.

3) identification of the pathophysiological role of the mineralocorticoid receptor in the vasculature and the control of blood pressure (2 papers) and implications in end-organ damages (kidney: immunosuppressor nephrotoxicity, ischemic injury; eye: retinopathies) with ongoing translational research (2 ongoing clinical trials for safety in kidney transplantation or efficacy in a particular retinal disease).

4) identification of novel target tissues of mineralocorticoids : skin (keratinocyte, hair follicle) and retina (4 publications, 2 patents) with major clinical perspectives and therapeutic innovations (wound healing, retinal oedema; 2 ongoing clinical trials in dermatology  and ophtalmology).
 
Team Head:  Frederic JAISSER, MD, PhD Frderic Jaisser
Dr JAISSER belongs to several research networks, including EU-granted programs. Since 2010, he is Scientific Delegate of the Pathophysiology Committee of the French National Research Agency.
He was recently appointed as Coordinator of a European Network on Aldosterone with more than 45 laboratories from 15 EU countries dedicated to the Aldosterone field, covering the continuum from experimental to clinical studies (http://www.admirecost.eu). He is part of the national F-CRIN INI-CRCT network dedicated to Cardiovascular and Renal Clinical Trialists (http://www.inicrct.org)



Team members:
Brigitte ESCOUBET (Dr), Nicolette FARMAN (Dr), Brian HARVEY (Dr).
Soumaya EL MOGHRABI (Eng).
Mathieu BUONAFINE (Doc),  Fouad FADEL (Doc), Lionel LATTENIST (Post-Doc), Sébastian LECHNER (Post-Doc), Ernesto MARTINEZ MARTINEZ (Post-Doc), Smaïl MESSAOUDI (Post-Doc), Van Tuan NGUYEN (Post-Doc), Thomas STEHLE (Doc).

Administration: Isabelle RICARD

Contact détails: 33 1 44 27 81 06 / Email: isabelle.ricard@crc.jussieu.fr


Selected publications

  • Barrera-Chimal J., Prince S., Fadel F., S. El Moghrabi1, D. G. Warnock, P. Kolkhof and F. Jaisser. Sulfenic acid modification of ET-B receptor is responsible for the benefit of   a non-steroidal MR antagonist in renal ischemia. JASN In Press
  • Tarjus, A. Fay R;  Farman N; Rossignol P, Zannad F; López-Andrés N; Jaisser F, Neutrophil Gelatinase Associated Lipocalin, a novel mineralocorticoid biotarget, mediates vascular pro-fibrotic effects of mineralocorticoids. Hypertension, 2015 In press. With editorial
  • Urbanet R; A. Nguyen Dinh Cat, A. Feraco, N. Venteclef, S. El Mogrhabi, C. Sierra-Ramos, D. Alvarez de la Rosa, G. K. Adler, D. Quilliot, P. Rossignol, F. Fallo, R. M Touyz; F Jaisser. Adipocyte mineralocorticoid receptor activation leads to metabolic syndrome and induction of Prostaglandin D2 Synthase. Hypertension. In press) With editorial
  • Zhao M, I. Celerier, E. Bousquet, J-C Jeanny, L.Jonet, M. Savoldelli, O. Offret, A. Curan, N.Farman*, F.Jaisser*,  F. Behar-Cohen*. Mineralocorticoid receptor activation leads to ocular choroidal vessel dilation in rats and human central serous chorioretinopathy. Journal of Clinical Investigation. 2012 * equally contributed
  • Galmiche G, Pizard A, Gueret A, El Moghrabi S, Ouvrard-Pascaud A, Berger S, Challande P, Jaffe IZ, Labat C, Lacolley P, Jaisser F. Smooth muscle cell mineralocorticoid receptors are mandatory for aldosterone-salt to induce vascular stiffness. Hypertension 2014 Mar;63(3):520-6

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