Finerenone protects against progression of kidney and cardiovascular damage in a model of type 1 diabetes through modulation of proinflammatory and osteogenic factors

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) ind...

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Authors: Sanz Gómez, Marta, Manzano Lista, Francisco Javier, Vega Martín, Elena, González Moreno, D., Alcalá, M., Gil Ortega, Marta, Somoza, Beatriz, Pizzamiglio, C., Ruilope Urioste, Luis Miguel, Aránguez, I., Kolkhof, P., Kreutz, R., Fernández Alfonso, María Soledad
Format: article
Publication Date:2023
Country:España
Institution:Universidad Complutense de Madrid (UCM)
Repository:Docta Complutense
Language:English
OAI Identifier:oai:docta.ucm.es:20.500.14352/110925
Online Access:https://hdl.handle.net/20.500.14352/110925
Access Level:Open access
Keyword:Chronic kidney disease
Type 1 diabetes
Streptozotocin
Finerenone
Bone morphogenetic proteins
Perivascular adipose tissue
Perirenal adipose tissue
Vascular disease
Farmacia
24 Ciencias de la Vida
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spelling Finerenone protects against progression of kidney and cardiovascular damage in a model of type 1 diabetes through modulation of proinflammatory and osteogenic factorsSanz Gómez, MartaManzano Lista, Francisco JavierVega Martín, ElenaGonzález Moreno, D.Alcalá, M.Gil Ortega, MartaSomoza, BeatrizPizzamiglio, C.Ruilope Urioste, Luis MiguelAránguez, I.Kolkhof, P.Kreutz, R.Fernández Alfonso, María SoledadChronic kidney diseaseType 1 diabetesStreptozotocinFinerenoneBone morphogenetic proteinsPerivascular adipose tissuePerirenal adipose tissueVascular diseaseFarmacia24 Ciencias de la VidaThe 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.ElsevierUniversidad Complutense de Madrid20232023-11-1120232023-11-11journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/110925reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/1109252026-06-02T12:44:21Z
dc.title.none.fl_str_mv Finerenone protects against progression of kidney and cardiovascular damage in a model of type 1 diabetes through modulation of proinflammatory and osteogenic factors
title Finerenone protects against progression of kidney and cardiovascular damage in a model of type 1 diabetes through modulation of proinflammatory and osteogenic factors
spellingShingle Finerenone protects against progression of kidney and cardiovascular damage in a model of type 1 diabetes through modulation of proinflammatory and osteogenic factors
Sanz Gómez, Marta
Chronic kidney disease
Type 1 diabetes
Streptozotocin
Finerenone
Bone morphogenetic proteins
Perivascular adipose tissue
Perirenal adipose tissue
Vascular disease
Farmacia
24 Ciencias de la Vida
title_short Finerenone protects against progression of kidney and cardiovascular damage in a model of type 1 diabetes through modulation of proinflammatory and osteogenic factors
title_full Finerenone protects against progression of kidney and cardiovascular damage in a model of type 1 diabetes through modulation of proinflammatory and osteogenic factors
title_fullStr Finerenone protects against progression of kidney and cardiovascular damage in a model of type 1 diabetes through modulation of proinflammatory and osteogenic factors
title_full_unstemmed Finerenone protects against progression of kidney and cardiovascular damage in a model of type 1 diabetes through modulation of proinflammatory and osteogenic factors
title_sort Finerenone protects against progression of kidney and cardiovascular damage in a model of type 1 diabetes through modulation of proinflammatory and osteogenic factors
dc.creator.none.fl_str_mv Sanz Gómez, Marta
Manzano Lista, Francisco Javier
Vega Martín, Elena
González Moreno, D.
Alcalá, M.
Gil Ortega, Marta
Somoza, Beatriz
Pizzamiglio, C.
Ruilope Urioste, Luis Miguel
Aránguez, I.
Kolkhof, P.
Kreutz, R.
Fernández Alfonso, María Soledad
author Sanz Gómez, Marta
author_facet Sanz Gómez, Marta
Manzano Lista, Francisco Javier
Vega Martín, Elena
González Moreno, D.
Alcalá, M.
Gil Ortega, Marta
Somoza, Beatriz
Pizzamiglio, C.
Ruilope Urioste, Luis Miguel
Aránguez, I.
Kolkhof, P.
Kreutz, R.
Fernández Alfonso, María Soledad
author_role author
author2 Manzano Lista, Francisco Javier
Vega Martín, Elena
González Moreno, D.
Alcalá, M.
Gil Ortega, Marta
Somoza, Beatriz
Pizzamiglio, C.
Ruilope Urioste, Luis Miguel
Aránguez, I.
Kolkhof, P.
Kreutz, R.
Fernández Alfonso, María Soledad
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv Chronic kidney disease
Type 1 diabetes
Streptozotocin
Finerenone
Bone morphogenetic proteins
Perivascular adipose tissue
Perirenal adipose tissue
Vascular disease
Farmacia
24 Ciencias de la Vida
topic Chronic kidney disease
Type 1 diabetes
Streptozotocin
Finerenone
Bone morphogenetic proteins
Perivascular adipose tissue
Perirenal adipose tissue
Vascular disease
Farmacia
24 Ciencias de la Vida
description 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.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-11-11
2023
2023-11-11
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/110925
url https://hdl.handle.net/20.500.14352/110925
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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