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- Publisher Website: 10.1161/HYPERTENSIONAHA.115.05431
- Scopus: eid_2-s2.0-84940025127
- PMID: 25987661
- WOS: WOS:000357080300024
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Article: Neutrophil gelatinase-associated lipocalin, a novel mineralocorticoid biotarget, mediates vascular profibrotic effects of mineralocorticoids
Title | Neutrophil gelatinase-associated lipocalin, a novel mineralocorticoid biotarget, mediates vascular profibrotic effects of mineralocorticoids |
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Authors | |
Keywords | lipocalin 2 mineralocorticoid receptor aldosterone collagen type I fibroblast |
Issue Date | 2015 |
Citation | Hypertension, 2015, v. 66, n. 1, p. 158-166 How to Cite? |
Abstract | © 2015 American Heart Association, Inc. Activation of the mineralocorticoid receptor has been shown to be deleterious in cardiovascular diseases (CVDs). We have recently shown that lipocalin 2 (Lcn2), or neutrophil gelatinase-associated lipocalin (NGAL), is a primary target of aldosterone/mineralocorticoid receptor in the cardiovascular system. Lcn2 is a circulating protein, which binds matrix metalloproteinase 9 and modulates its stability. We hypothesized that Lcn2 could be a mediator of aldosterone/mineralocorticoid receptor profibrotic effects in the cardiovascular system. Correlations between aldosterone and profibrotic markers, such as procollagen type I N-terminal peptide, were investigated in healthy subjects and subjects with abdominal obesity. The implication of Lcn2 in the mineralocorticoid pathway was studied using Lcn2 knockout mice subjected to a nephrectomy/aldosterone/salt (NAS) challenge for 4 weeks. In human subjects, NGAL/matrix metalloproteinase 9 was positively correlated with plasma aldosterone and fibrosis biomarkers. In mice, loss of Lcn2 prevented the NAS-induced increase of plasma procollagen type I N-terminal peptide, as well as the increase of collagen fibers deposition and collagen I expression in the coronary vessels and the aorta. The lack of Lcn2 also blunted the NAS-induced increase in systolic blood pressure. Ex vivo, treatment of human fibroblasts with recombinant Lcn2 induced the expression of collagen I and the profibrotic galectin-3 and cardiotrophin-1 molecules. Our results showed that Lcn2 plays a key role in aldosterone/mineralocorticoid receptor-mediated vascular fibrosis. The clinical data indicate that this may translate in human patients. Lcn2 is, therefore, a new biotarget in cardiovascular fibrosis induced by mineralocorticoid activation. |
Persistent Identifier | http://hdl.handle.net/10722/292900 |
ISSN | 2023 Impact Factor: 6.9 2023 SCImago Journal Rankings: 2.827 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Tarjus, Antoine | - |
dc.contributor.author | Martínez-Martínez, Ernesto | - |
dc.contributor.author | Amador, Cristian | - |
dc.contributor.author | Latouche, Céline | - |
dc.contributor.author | El Moghrabi, Soumaya | - |
dc.contributor.author | Berger, Thorsten | - |
dc.contributor.author | Mak, Tak W. | - |
dc.contributor.author | Fay, Renaud | - |
dc.contributor.author | Farman, Nicolette | - |
dc.contributor.author | Rossignol, Patrick | - |
dc.contributor.author | Zannad, Faiez | - |
dc.contributor.author | López-Andrés, Natalia | - |
dc.contributor.author | Jaisser, Frédéric | - |
dc.date.accessioned | 2020-11-17T14:57:27Z | - |
dc.date.available | 2020-11-17T14:57:27Z | - |
dc.date.issued | 2015 | - |
dc.identifier.citation | Hypertension, 2015, v. 66, n. 1, p. 158-166 | - |
dc.identifier.issn | 0194-911X | - |
dc.identifier.uri | http://hdl.handle.net/10722/292900 | - |
dc.description.abstract | © 2015 American Heart Association, Inc. Activation of the mineralocorticoid receptor has been shown to be deleterious in cardiovascular diseases (CVDs). We have recently shown that lipocalin 2 (Lcn2), or neutrophil gelatinase-associated lipocalin (NGAL), is a primary target of aldosterone/mineralocorticoid receptor in the cardiovascular system. Lcn2 is a circulating protein, which binds matrix metalloproteinase 9 and modulates its stability. We hypothesized that Lcn2 could be a mediator of aldosterone/mineralocorticoid receptor profibrotic effects in the cardiovascular system. Correlations between aldosterone and profibrotic markers, such as procollagen type I N-terminal peptide, were investigated in healthy subjects and subjects with abdominal obesity. The implication of Lcn2 in the mineralocorticoid pathway was studied using Lcn2 knockout mice subjected to a nephrectomy/aldosterone/salt (NAS) challenge for 4 weeks. In human subjects, NGAL/matrix metalloproteinase 9 was positively correlated with plasma aldosterone and fibrosis biomarkers. In mice, loss of Lcn2 prevented the NAS-induced increase of plasma procollagen type I N-terminal peptide, as well as the increase of collagen fibers deposition and collagen I expression in the coronary vessels and the aorta. The lack of Lcn2 also blunted the NAS-induced increase in systolic blood pressure. Ex vivo, treatment of human fibroblasts with recombinant Lcn2 induced the expression of collagen I and the profibrotic galectin-3 and cardiotrophin-1 molecules. Our results showed that Lcn2 plays a key role in aldosterone/mineralocorticoid receptor-mediated vascular fibrosis. The clinical data indicate that this may translate in human patients. Lcn2 is, therefore, a new biotarget in cardiovascular fibrosis induced by mineralocorticoid activation. | - |
dc.language | eng | - |
dc.relation.ispartof | Hypertension | - |
dc.subject | lipocalin 2 | - |
dc.subject | mineralocorticoid receptor | - |
dc.subject | aldosterone | - |
dc.subject | collagen type I | - |
dc.subject | fibroblast | - |
dc.title | Neutrophil gelatinase-associated lipocalin, a novel mineralocorticoid biotarget, mediates vascular profibrotic effects of mineralocorticoids | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1161/HYPERTENSIONAHA.115.05431 | - |
dc.identifier.pmid | 25987661 | - |
dc.identifier.scopus | eid_2-s2.0-84940025127 | - |
dc.identifier.volume | 66 | - |
dc.identifier.issue | 1 | - |
dc.identifier.spage | 158 | - |
dc.identifier.epage | 166 | - |
dc.identifier.eissn | 1524-4563 | - |
dc.identifier.isi | WOS:000357080300024 | - |
dc.identifier.issnl | 0194-911X | - |