In:
Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 74, No. Suppl_1 ( 2019-09)
Abstract:
Introduction: Neutrophil Gelatinase-Associated Lipocalin (NGAL) (or lipocalin 2) is a novel mineralocorticoid biotarget in the cardiovascular system. NGAL is also described as an acute renal lesion biomarker and NGAL serum concentration is associated with the severity of renal damages patients with a chronic kidney disease (CKD). Lipocalin2 (Lcn2) gene invalidation in a CKD mouse model protects from proteinuria and renal lesions. Objective: Since the immune system is involved in renal inflammation and fibrosis process, we hypothesized that the production of NGAL/Lcn2 by immune cells plays an important role in the deleterious mineralocorticoid effects in the kidney. Methods: The role of Lcn2 produced by immune cells was analyzed using full Lcn2 knock out mice (Full KO) and mice depleted for Lcn2 in their immune cells by bone marrow transplantation (BMT lcn2 KO). These mice were challenged with uni-Nephrectomy, Aldosterone 200μg/kg/day, Salt 1% (NAS model) during 6 weeks. Results: NAS induced a significant increase in the expression (relative values, mean±SEM, compared to 1 in the control samples, p 〈 0.05, n=6-9) of proinflammatory proteins such as MCP-1 (5.00±0.26), TNF-α (8.58±0.31), OPN (1.60±0.07), RANTES (3.98±0.20) and extracellular matrix proteins such as collagen IV (1.94±0.10), α-SMA (2.04±0.13) and fibronectin (3.38±0.20) in the kidney of WT mice. This effect was blunted in both KO mouse models (Full KO and BMT KO). Kidney fibrosis was induced by NAS (relative values, mean±SEM, compared to 1 in the control samples, p 〈 0.05, n= 6-9) (5.98±0.19). this increase was fully prevented in Full KO NAS mice and partly corrected in BMT KO NAS mice. Macrophages isolated from Full Lcn2 KO or WT mice were co-treated with aldosterone (10 -8 M) and NaCl (40mM). In WT macrophages, mRNA expression (relative values, mean±SEM, compared to 1 in the control samples, p 〈 0.05, n=6) of Lcn2 (22.06±1.36) as well as a the RANTES/CCl5 chemokine (10.88±0.88) is increased. The increase of RANTES/CCl5 was fully blunted in Lcn2 KO macrophages. Conclusion: NGAL produced by immune cells plays a critical role in renal interstitial fibrosis and inflammation induced by mineralocorticoid excess. The role of RANTES/CCl5 in the renal NGAL-mineralocorticoid pathways is currently analyzed.
Type of Medium:
Online Resource
ISSN:
0194-911X
,
1524-4563
DOI:
10.1161/hyp.74.suppl_1.010
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2019
detail.hit.zdb_id:
2094210-2
