Aldosterone Target NGAL (Neutrophil Gelatinase–Associated Lipocalin) Is Involved in Cardiac Remodeling After Myocardial Infarction Through NFκB Pathway

• DOI: 10.1161/hypertensionaha.117.09791
• Publication Date: 2017-10-24T00:10:34Z
• Authors: Ernesto Martínez-...; Mathieu Buonafine; Ines Boukhalfa; Jaime Ibarrola; Amaya Fernández-C...; Peter Kolkhof; Patrick Rossignol; Nicolas Girerd; Paul Mulder; Natalia López-Andrés; Antoine Ouvrard-P...; Frédéric Jaisser
• Keywords: Cardiac Fibrosis; Mineralocorticoid

Myocardial infarction (MI) is accompanied by cardiac fibrosis, which contributes to dysfunction. Mineralocorticoid receptor (MR) antagonists have beneficial effects in patients with left ventricular (LV) dysfunction after MI. We herein investigated the role of MR target NGAL (neutrophil gelatinase–associated lipocalin) post-MI damages. Both higher baseline and a greater increase serum levels during follow-up were significantly associated lower 6-month LV ejection fraction recovery cohort 119 patients, as assessed magnetic resonance imaging. protein increased at 7 days wild-type mice This effect was prevented treatment nonsteroidal antagonist finerenone (1 mg/kg per day). knockout MI had interstitial fibrosis inflammation, better contractility compliance, stroke volume output than 3 months post-MI. Aldosterone (10 −8 mol/L) expression cultured human fibroblasts. Cells treated aldosterone or (500 ng/mL) showed production collagen type I. The abolished −6 knockdown. NGAL-mediated activity relied on NFκB (nuclear factor-κB) activation, confirmed use NFκB-specific inhibitor BAY11-7082, both I production. In conclusion, NGAL, downstream activation target, key mediator damage. may be potential therapeutic cardiovascular pathological situations involved.