Loxin Reduced the Inflammatory Response in the Liver and the Aortic Fatty Streak Formation in Mice Fed with a High-Fat Diet
Oxidized low-density lipoprotein (ox-LDL) is the most harmful form of cholesterol associated with vascular atherosclerosis and hepatic injury, mainly due to inflammatory cell infiltration and subsequent severe tissue injury. Lox-1 is the central ox-LDL receptor expressed in endothelial and immune ce...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266330/ https://www.ncbi.nlm.nih.gov/pubmed/35806336 http://dx.doi.org/10.3390/ijms23137329 |
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author | Reyes, Camila Nova-Lamperti, Estefanía Duran-Sandoval, Daniel Rojas, Daniela Gajardo, Jorge Guzman-Gutierrez, Enrique Bustos-Ruiz, Camila Ormazábal, Valeska Zúñiga, Felipe A. Escudero, Carlos Aguayo, Claudio |
author_facet | Reyes, Camila Nova-Lamperti, Estefanía Duran-Sandoval, Daniel Rojas, Daniela Gajardo, Jorge Guzman-Gutierrez, Enrique Bustos-Ruiz, Camila Ormazábal, Valeska Zúñiga, Felipe A. Escudero, Carlos Aguayo, Claudio |
author_sort | Reyes, Camila |
collection | PubMed |
description | Oxidized low-density lipoprotein (ox-LDL) is the most harmful form of cholesterol associated with vascular atherosclerosis and hepatic injury, mainly due to inflammatory cell infiltration and subsequent severe tissue injury. Lox-1 is the central ox-LDL receptor expressed in endothelial and immune cells, its activation regulating inflammatory cytokines and chemotactic factor secretion. Recently, a Lox-1 truncated protein isoform lacking the ox-LDL binding domain named LOXIN has been described. We have previously shown that LOXIN overexpression blocked Lox-1-mediated ox-LDL internalization in human endothelial progenitor cells in vitro. However, the functional role of LOXIN in targeting inflammation or tissue injury in vivo remains unknown. In this study, we investigate whether LOXIN modulated the expression of Lox-1 and reduced the inflammatory response in a high-fat-diet mice model. Results indicate that human LOXIN blocks Lox-1 mediated uptake of ox-LDL in H4-II-E-C3 cells. Furthermore, in vivo experiments showed that overexpression of LOXIN reduced both fatty streak lesions in the aorta and inflammation and fibrosis in the liver. These findings were associated with the down-regulation of Lox-1 in endothelial cells. Then, LOXIN prevents hepatic and aortic tissue damage in vivo associated with reduced Lox-1 expression in endothelial cells. We encourage future research to understand better the underlying molecular mechanisms and potential therapeutic use of LOXIN. |
format | Online Article Text |
id | pubmed-9266330 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-92663302022-07-09 Loxin Reduced the Inflammatory Response in the Liver and the Aortic Fatty Streak Formation in Mice Fed with a High-Fat Diet Reyes, Camila Nova-Lamperti, Estefanía Duran-Sandoval, Daniel Rojas, Daniela Gajardo, Jorge Guzman-Gutierrez, Enrique Bustos-Ruiz, Camila Ormazábal, Valeska Zúñiga, Felipe A. Escudero, Carlos Aguayo, Claudio Int J Mol Sci Article Oxidized low-density lipoprotein (ox-LDL) is the most harmful form of cholesterol associated with vascular atherosclerosis and hepatic injury, mainly due to inflammatory cell infiltration and subsequent severe tissue injury. Lox-1 is the central ox-LDL receptor expressed in endothelial and immune cells, its activation regulating inflammatory cytokines and chemotactic factor secretion. Recently, a Lox-1 truncated protein isoform lacking the ox-LDL binding domain named LOXIN has been described. We have previously shown that LOXIN overexpression blocked Lox-1-mediated ox-LDL internalization in human endothelial progenitor cells in vitro. However, the functional role of LOXIN in targeting inflammation or tissue injury in vivo remains unknown. In this study, we investigate whether LOXIN modulated the expression of Lox-1 and reduced the inflammatory response in a high-fat-diet mice model. Results indicate that human LOXIN blocks Lox-1 mediated uptake of ox-LDL in H4-II-E-C3 cells. Furthermore, in vivo experiments showed that overexpression of LOXIN reduced both fatty streak lesions in the aorta and inflammation and fibrosis in the liver. These findings were associated with the down-regulation of Lox-1 in endothelial cells. Then, LOXIN prevents hepatic and aortic tissue damage in vivo associated with reduced Lox-1 expression in endothelial cells. We encourage future research to understand better the underlying molecular mechanisms and potential therapeutic use of LOXIN. MDPI 2022-06-30 /pmc/articles/PMC9266330/ /pubmed/35806336 http://dx.doi.org/10.3390/ijms23137329 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Reyes, Camila Nova-Lamperti, Estefanía Duran-Sandoval, Daniel Rojas, Daniela Gajardo, Jorge Guzman-Gutierrez, Enrique Bustos-Ruiz, Camila Ormazábal, Valeska Zúñiga, Felipe A. Escudero, Carlos Aguayo, Claudio Loxin Reduced the Inflammatory Response in the Liver and the Aortic Fatty Streak Formation in Mice Fed with a High-Fat Diet |
title | Loxin Reduced the Inflammatory Response in the Liver and the Aortic Fatty Streak Formation in Mice Fed with a High-Fat Diet |
title_full | Loxin Reduced the Inflammatory Response in the Liver and the Aortic Fatty Streak Formation in Mice Fed with a High-Fat Diet |
title_fullStr | Loxin Reduced the Inflammatory Response in the Liver and the Aortic Fatty Streak Formation in Mice Fed with a High-Fat Diet |
title_full_unstemmed | Loxin Reduced the Inflammatory Response in the Liver and the Aortic Fatty Streak Formation in Mice Fed with a High-Fat Diet |
title_short | Loxin Reduced the Inflammatory Response in the Liver and the Aortic Fatty Streak Formation in Mice Fed with a High-Fat Diet |
title_sort | loxin reduced the inflammatory response in the liver and the aortic fatty streak formation in mice fed with a high-fat diet |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266330/ https://www.ncbi.nlm.nih.gov/pubmed/35806336 http://dx.doi.org/10.3390/ijms23137329 |
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