Dendritic cells are crucial for cardiovascular remodeling and modulate neutrophil gelatinase-associated lipocalin expression upon mineralocorticoid receptor activation

Patricio Araos; Carolina Prado; Mauricio Lozano; Stefanny Figueroa; Alexandra Espinoza; Thorsten Berger; Tak W. Mak; Frédéric Jaisser; Rodrigo Pacheco; Luis Michea; Cristián A. Amador

doi:10.1097/HJH.0000000000002067

Dendritic cells are crucial for cardiovascular remodeling and modulate neutrophil gelatinase-associated lipocalin expression upon mineralocorticoid receptor activation

Patricio Araos, Carolina Prado, Mauricio Lozano, Stefanny Figueroa, Alexandra Espinoza, Thorsten Berger, Tak W. Mak, Frédéric Jaisser, Rodrigo Pacheco, Luis Michea, Cristián A. Amador^*

^*Corresponding author for this work

Fundación Ciencia para la Vida

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

Background:Adaptive immunity is crucial in cardiovascular and renal inflammation/fibrosis upon hyperactivation of mineralocorticoid receptor. We have previously demonstrated that dendritic cells can respond to mineralocorticoid receptor activation, and the neutrophil gelatinase-associated lipocalin (NGAL) in dendritic cells is highly increased during aldosterone (Aldo)/mineralocorticoid receptor-dependent cardiovascular damage. However, the interrelationship among dendritic cells, target organs inflammation/fibrosis induced by mineralocorticoid receptor, and NGAL-dependence remains unknown.Objective:We studied the role of dendritic cells in mineralocorticoid receptor-dependent tissue remodeling and whether NGAL can modulate the inflammatory response of dendritic cells after mineralocorticoid receptor activation.Methods:Cardiovascular and renal remodeling induced by Aldo and high-salt diet [nephrectomy-Aldo-salt (NAS) model] were analyzed in CD11c.DOG mice, a model which allows dendritic cells ablation by using diphtheria toxin. In addition, in-vitro studies in NGAL-knock out dendritic cells were performed to determine the immunomodulatory role of NGAL upon Aldo treatment.Results:The ablation of dendritic cells prevented the development of cardiac hypertrophy, perivascular fibrosis, and the overexpression of NGAL, brain natriuretic peptide, and two profibrotic factors induced by NAS: collagen 1A1 and connective tissue growth factor. We determined that dendritic cells were not required to prevent renal hypertrophy/fibrosis induced by NAS. Between different immune cells analyzed, we observed that NGAL abundance was higher in antigen-presenting cells, while in-vitro studies showed that mineralocorticoid receptor stimulation in dendritic cells favored NGAL and IL-23 expression (p19 and p40 subunits), which are involved in the development of fibrosis and the Th17-driven response, respectively.Conclusion:NGAL produced by dendritic cells may play a pivotal role in the activation of adaptive immunity that leads to cardiovascular fibrosis during mineralocorticoids excess.

Original language	English
Pages (from-to)	1482-1492
Number of pages	11
Journal	Journal of Hypertension
Volume	37
Issue number	7
DOIs	https://doi.org/10.1097/HJH.0000000000002067
State	Published - 2019

Bibliographical note

Funding Information:
The work was supported by FONDECYT Iniciación 11150542 (C.A.A.), CONICYT-Doctorado 21130482 (P.A.), FONDECYT-Postdoctorado 3160383 (C.P.), FONDECYT-Regular grants 1130550 and 1171869 (L.M.), 1170093 (R.P.), CONICYT-Basal AFB 170004 (R.P.), The Millennium Institute on Immunology and Immunotherapy (MIII; P09/ 016-F ICM), Fondation de France (2014-00047968), ANR MRFOCUS (ANR-15-CE14-0032-02), and the Fight-HF Avenir investment program (ANR-15-RHUS-0004) (F.J.).

Publisher Copyright:
© 2019 Wolters Kluwer Health, Inc. All rights reserved.

ASJC Scopus subject areas

Internal Medicine
Physiology
Cardiology and Cardiovascular Medicine

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10.1097/HJH.0000000000002067

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Araos, P., Prado, C., Lozano, M., Figueroa, S., Espinoza, A., Berger, T., Mak, T. W., Jaisser, F., Pacheco, R., Michea, L., & Amador, C. A. (2019). Dendritic cells are crucial for cardiovascular remodeling and modulate neutrophil gelatinase-associated lipocalin expression upon mineralocorticoid receptor activation. Journal of Hypertension, 37(7), 1482-1492. https://doi.org/10.1097/HJH.0000000000002067

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title = "Dendritic cells are crucial for cardiovascular remodeling and modulate neutrophil gelatinase-associated lipocalin expression upon mineralocorticoid receptor activation",

abstract = "Background:Adaptive immunity is crucial in cardiovascular and renal inflammation/fibrosis upon hyperactivation of mineralocorticoid receptor. We have previously demonstrated that dendritic cells can respond to mineralocorticoid receptor activation, and the neutrophil gelatinase-associated lipocalin (NGAL) in dendritic cells is highly increased during aldosterone (Aldo)/mineralocorticoid receptor-dependent cardiovascular damage. However, the interrelationship among dendritic cells, target organs inflammation/fibrosis induced by mineralocorticoid receptor, and NGAL-dependence remains unknown.Objective:We studied the role of dendritic cells in mineralocorticoid receptor-dependent tissue remodeling and whether NGAL can modulate the inflammatory response of dendritic cells after mineralocorticoid receptor activation.Methods:Cardiovascular and renal remodeling induced by Aldo and high-salt diet [nephrectomy-Aldo-salt (NAS) model] were analyzed in CD11c.DOG mice, a model which allows dendritic cells ablation by using diphtheria toxin. In addition, in-vitro studies in NGAL-knock out dendritic cells were performed to determine the immunomodulatory role of NGAL upon Aldo treatment.Results:The ablation of dendritic cells prevented the development of cardiac hypertrophy, perivascular fibrosis, and the overexpression of NGAL, brain natriuretic peptide, and two profibrotic factors induced by NAS: collagen 1A1 and connective tissue growth factor. We determined that dendritic cells were not required to prevent renal hypertrophy/fibrosis induced by NAS. Between different immune cells analyzed, we observed that NGAL abundance was higher in antigen-presenting cells, while in-vitro studies showed that mineralocorticoid receptor stimulation in dendritic cells favored NGAL and IL-23 expression (p19 and p40 subunits), which are involved in the development of fibrosis and the Th17-driven response, respectively.Conclusion:NGAL produced by dendritic cells may play a pivotal role in the activation of adaptive immunity that leads to cardiovascular fibrosis during mineralocorticoids excess.",

keywords = "cardiovascular fibrosis, dendritic cells, inflammation, mineralocorticoid receptor, neutrophil gelatinase-associated lipocalin",

author = "Patricio Araos and Carolina Prado and Mauricio Lozano and Stefanny Figueroa and Alexandra Espinoza and Thorsten Berger and Mak, {Tak W.} and Fr{\'e}d{\'e}ric Jaisser and Rodrigo Pacheco and Luis Michea and Amador, {Cristi{\'a}n A.}",

note = "Funding Information: The work was supported by FONDECYT Iniciaci{\'o}n 11150542 (C.A.A.), CONICYT-Doctorado 21130482 (P.A.), FONDECYT-Postdoctorado 3160383 (C.P.), FONDECYT-Regular grants 1130550 and 1171869 (L.M.), 1170093 (R.P.), CONICYT-Basal AFB 170004 (R.P.), The Millennium Institute on Immunology and Immunotherapy (MIII; P09/ 016-F ICM), Fondation de France (2014-00047968), ANR MRFOCUS (ANR-15-CE14-0032-02), and the Fight-HF Avenir investment program (ANR-15-RHUS-0004) (F.J.). Publisher Copyright: {\textcopyright} 2019 Wolters Kluwer Health, Inc. All rights reserved.",

year = "2019",

month = jul,

day = "1",

doi = "10.1097/HJH.0000000000002067",

language = "English",

volume = "37",

pages = "1482--1492",

journal = "Journal of Hypertension",

issn = "0263-6352",

publisher = "Lippincott Williams and Wilkins",

number = "7",

}

Araos, P, Prado, C, Lozano, M, Figueroa, S, Espinoza, A, Berger, T, Mak, TW, Jaisser, F, Pacheco, R, Michea, L & Amador, CA 2019, 'Dendritic cells are crucial for cardiovascular remodeling and modulate neutrophil gelatinase-associated lipocalin expression upon mineralocorticoid receptor activation', Journal of Hypertension, vol. 37, no. 7, pp. 1482-1492. https://doi.org/10.1097/HJH.0000000000002067

TY - JOUR

T1 - Dendritic cells are crucial for cardiovascular remodeling and modulate neutrophil gelatinase-associated lipocalin expression upon mineralocorticoid receptor activation

AU - Araos, Patricio

AU - Prado, Carolina

AU - Lozano, Mauricio

AU - Figueroa, Stefanny

AU - Espinoza, Alexandra

AU - Berger, Thorsten

AU - Mak, Tak W.

AU - Jaisser, Frédéric

AU - Pacheco, Rodrigo

AU - Michea, Luis

AU - Amador, Cristián A.

N1 - Funding Information: The work was supported by FONDECYT Iniciación 11150542 (C.A.A.), CONICYT-Doctorado 21130482 (P.A.), FONDECYT-Postdoctorado 3160383 (C.P.), FONDECYT-Regular grants 1130550 and 1171869 (L.M.), 1170093 (R.P.), CONICYT-Basal AFB 170004 (R.P.), The Millennium Institute on Immunology and Immunotherapy (MIII; P09/ 016-F ICM), Fondation de France (2014-00047968), ANR MRFOCUS (ANR-15-CE14-0032-02), and the Fight-HF Avenir investment program (ANR-15-RHUS-0004) (F.J.). Publisher Copyright: © 2019 Wolters Kluwer Health, Inc. All rights reserved.

PY - 2019/7/1

Y1 - 2019/7/1

N2 - Background:Adaptive immunity is crucial in cardiovascular and renal inflammation/fibrosis upon hyperactivation of mineralocorticoid receptor. We have previously demonstrated that dendritic cells can respond to mineralocorticoid receptor activation, and the neutrophil gelatinase-associated lipocalin (NGAL) in dendritic cells is highly increased during aldosterone (Aldo)/mineralocorticoid receptor-dependent cardiovascular damage. However, the interrelationship among dendritic cells, target organs inflammation/fibrosis induced by mineralocorticoid receptor, and NGAL-dependence remains unknown.Objective:We studied the role of dendritic cells in mineralocorticoid receptor-dependent tissue remodeling and whether NGAL can modulate the inflammatory response of dendritic cells after mineralocorticoid receptor activation.Methods:Cardiovascular and renal remodeling induced by Aldo and high-salt diet [nephrectomy-Aldo-salt (NAS) model] were analyzed in CD11c.DOG mice, a model which allows dendritic cells ablation by using diphtheria toxin. In addition, in-vitro studies in NGAL-knock out dendritic cells were performed to determine the immunomodulatory role of NGAL upon Aldo treatment.Results:The ablation of dendritic cells prevented the development of cardiac hypertrophy, perivascular fibrosis, and the overexpression of NGAL, brain natriuretic peptide, and two profibrotic factors induced by NAS: collagen 1A1 and connective tissue growth factor. We determined that dendritic cells were not required to prevent renal hypertrophy/fibrosis induced by NAS. Between different immune cells analyzed, we observed that NGAL abundance was higher in antigen-presenting cells, while in-vitro studies showed that mineralocorticoid receptor stimulation in dendritic cells favored NGAL and IL-23 expression (p19 and p40 subunits), which are involved in the development of fibrosis and the Th17-driven response, respectively.Conclusion:NGAL produced by dendritic cells may play a pivotal role in the activation of adaptive immunity that leads to cardiovascular fibrosis during mineralocorticoids excess.

AB - Background:Adaptive immunity is crucial in cardiovascular and renal inflammation/fibrosis upon hyperactivation of mineralocorticoid receptor. We have previously demonstrated that dendritic cells can respond to mineralocorticoid receptor activation, and the neutrophil gelatinase-associated lipocalin (NGAL) in dendritic cells is highly increased during aldosterone (Aldo)/mineralocorticoid receptor-dependent cardiovascular damage. However, the interrelationship among dendritic cells, target organs inflammation/fibrosis induced by mineralocorticoid receptor, and NGAL-dependence remains unknown.Objective:We studied the role of dendritic cells in mineralocorticoid receptor-dependent tissue remodeling and whether NGAL can modulate the inflammatory response of dendritic cells after mineralocorticoid receptor activation.Methods:Cardiovascular and renal remodeling induced by Aldo and high-salt diet [nephrectomy-Aldo-salt (NAS) model] were analyzed in CD11c.DOG mice, a model which allows dendritic cells ablation by using diphtheria toxin. In addition, in-vitro studies in NGAL-knock out dendritic cells were performed to determine the immunomodulatory role of NGAL upon Aldo treatment.Results:The ablation of dendritic cells prevented the development of cardiac hypertrophy, perivascular fibrosis, and the overexpression of NGAL, brain natriuretic peptide, and two profibrotic factors induced by NAS: collagen 1A1 and connective tissue growth factor. We determined that dendritic cells were not required to prevent renal hypertrophy/fibrosis induced by NAS. Between different immune cells analyzed, we observed that NGAL abundance was higher in antigen-presenting cells, while in-vitro studies showed that mineralocorticoid receptor stimulation in dendritic cells favored NGAL and IL-23 expression (p19 and p40 subunits), which are involved in the development of fibrosis and the Th17-driven response, respectively.Conclusion:NGAL produced by dendritic cells may play a pivotal role in the activation of adaptive immunity that leads to cardiovascular fibrosis during mineralocorticoids excess.

KW - cardiovascular fibrosis

KW - dendritic cells

KW - inflammation

KW - mineralocorticoid receptor

KW - neutrophil gelatinase-associated lipocalin

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U2 - 10.1097/HJH.0000000000002067

DO - 10.1097/HJH.0000000000002067

M3 - Article

C2 - 31033725

AN - SCOPUS:85067269649

SN - 0263-6352

VL - 37

SP - 1482

EP - 1492

JO - Journal of Hypertension

JF - Journal of Hypertension

IS - 7

ER -

Dendritic cells are crucial for cardiovascular remodeling and modulate neutrophil gelatinase-associated lipocalin expression upon mineralocorticoid receptor activation

Abstract

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