RT Journal Article
T1 Finerenone protects against progression of kidney and cardiovascular damage in a model of type 1 diabetes through modulation of proinflammatory and osteogenic factors
A1 Sanz Gómez, Marta
A1 Manzano Lista, Francisco Javier
A1 Vega Martín, Elena
A1 González Moreno, D.
A1 Alcalá, M.
A1 Gil Ortega, Marta
A1 Somoza, Beatriz
A1 Pizzamiglio, C.
A1 Ruilope Urioste, Luis Miguel
A1 Aránguez, I.
A1 Kolkhof, P.
A1 Kreutz, R.
A1 Fernández Alfonso, María Soledad
AB The non-steroidal mineralocorticoid receptor antagonist (MRA) finerenone (FIN) improves kidney and cardiovascular outcomes in patients with chronic kidney disease (CKD) in type 2 diabetes (T2D). We explored the effect of FIN in a novel model of type 1 diabetic Munich Wistar Frömter (MWF) rat (D) induced by injection of streptozotocin (15 mg/kg) and additional exposure to a high-fat/high-sucrose diet. Oral treatment with FIN (10 mg/kg/day in rat chow) in diabetic animals (D-FIN) was compared to a group of D rats receiving no treatment and a group of non-diabetic untreated MWF rats (C) (n = 7–10 animals per group). After 6 weeks, D and D-FIN exhibited significantly elevated blood glucose levels (271.7 ± 67.1 mg/dl and 266.3 ± 46.8 mg/dl) as compared to C (110.3 ± 4.4 mg/dl; p < 0.05). D showed a 10-fold increase of kidney damage markers Kim-1 and Ngal which was significantly suppressed in D-FIN. Blood pressure, pulse wave velocity (PWV) and arterial collagen deposition were lower in D-FIN, associated to an improvement in endothelial function due to a reduction in pro-contractile prostaglandins, as well as reactive oxygen species (ROS) and inflammatory cytokines (IL-1, IL-6, TNFα and TGFβ) in perivascular and perirenal adipose tissue (PVAT and PRAT, respectively). In addition, FIN restored the imbalance observed in CKD between the procalcifying BMP-2 and the nephroprotective BMP-7 in plasma, kidney, PVAT, and PRAT. Our data show that treatment with FIN improves kidney and vascular damage in a new rat model of DKD with T1D associated with a reduction in inflammation, fibrosis and osteogenic factors independently from changes in glucose homeostasis.
PB Elsevier
SN 0753-3322
YR 2023
FD 2023-11-11
LK https://hdl.handle.net/20.500.14352/110925
UL https://hdl.handle.net/20.500.14352/110925
LA eng
NO M. Sanz-Gómez, F.J. Manzano-Lista, E. Vega-Martín, D. González-Moreno, M. Alcalá, M. Gil-Ortega, B. Somoza, C. Pizzamiglio, L.M. Ruilope, I. Aránguez, P. Kolkhof, R. Kreutz, M.S. Fernández-Alfonso, Finerenone protects against progression of kidney and cardiovascular damage in a model of type 1 diabetes through modulation of proinflammatory and osteogenic factors, Biomedicine & Pharmacotherapy, Volume 168, 2023, 115661, https://doi.org/10.1016/j.biopha.2023.115661.
NO 2023 Acuerdos transformativos CRUE
NO European Commission
DS Docta Complutense
RD 6 abr 2025