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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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