title: Neutrophil gelatinase-associated lipocalin is a novel mineralocorticoid target in the cardiovascular system.
abstract: Mineralocorticoid receptor (MR) activation may be deleterious to the cardiovascular system, and MR antagonists improve morbidity and mortality of patients with heart failure. However, mineralocorticoid signaling in the heart remains largely unknown. Using a pan-genomic transcriptomic analysis, we identified neutrophil gelatinase-associated lipocalin (NGAL or lipocalin 2) as a strongly induced gene in the heart of mice with conditional and targeted MR overexpression in cardiomyocytes (whereas induction was low in glucocorticoid receptor-overexpressing mice). NGAL mRNA levels were enhanced after hormonal stimulation by the MR ligand aldosterone in cultured cardiac cells and in the heart of wild-type mice. Mineralocorticoid pathological challenge induced by nephrectomy/aldosterone/salt treatment upregulated NGAL expression in the heart and aorta and its plasma levels. We show evidence for MR binding to an NGAL promoter, providing a mechanism for NGAL regulation. We propose that NGAL may be a marker of mineralocorticoid-dependent injury in the cardiovascular system in mice.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale UMR 872 Team 1, Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Paris, France.
authors.forename: Celine
authors.initials: C
authors.lastname: Latouche
authors.forename: Soumaya
authors.initials: S
authors.lastname: El Moghrabi
authors.forename: Smail
authors.initials: S
authors.lastname: Messaoudi
authors.forename: Aurélie
authors.initials: A
authors.lastname: Nguyen Dinh Cat
authors.forename: Ivan
authors.initials: I
authors.lastname: Hernandez-Diaz
authors.forename: Diego
authors.initials: D
authors.lastname: Alvarez de la Rosa
authors.forename: Claudine
authors.initials: C
authors.lastname: Perret
authors.forename: Natalia
authors.initials: N
authors.lastname: López Andrés
authors.forename: Patrick
authors.initials: P
authors.lastname: Rossignol
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.forename: Nicolette
authors.initials: N
authors.lastname: Farman
authors.forename: Frederic
authors.initials: F
authors.lastname: Jaisser
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002319:Cardiovascular System / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000378:metabolism*; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D000209:Acute-Phase Proteins; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; C071332:Lcn2 protein, mouse