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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MDPI AG
2022-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/13/7329 |
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| author | Camila Reyes Estefanía Nova-Lamperti Daniel Duran-Sandoval Daniela Rojas Jorge Gajardo Enrique Guzman-Gutierrez Camila Bustos-Ruiz Valeska Ormazábal Felipe A. Zúñiga Carlos Escudero Claudio Aguayo |
| author_facet | Camila Reyes Estefanía Nova-Lamperti Daniel Duran-Sandoval Daniela Rojas Jorge Gajardo Enrique Guzman-Gutierrez Camila Bustos-Ruiz Valeska Ormazábal Felipe A. Zúñiga Carlos Escudero Claudio Aguayo |
| author_sort | Camila Reyes |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T21:48:25Z |
| format | Article |
| id | doaj.art-e1462e68f13e46df8298f7b21808b355 |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:48:25Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e1462e68f13e46df8298f7b21808b3552023-11-23T20:12:00ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-06-012313732910.3390/ijms23137329Loxin Reduced the Inflammatory Response in the Liver and the Aortic Fatty Streak Formation in Mice Fed with a High-Fat DietCamila Reyes0Estefanía Nova-Lamperti1Daniel Duran-Sandoval2Daniela Rojas3Jorge Gajardo4Enrique Guzman-Gutierrez5Camila Bustos-Ruiz6Valeska Ormazábal7Felipe A. Zúñiga8Carlos Escudero9Claudio Aguayo10Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepcion, Concepción 4030000, ChileDepartment of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepcion, Concepción 4030000, ChileDepartment of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepcion, Concepción 4030000, ChileDepartment of Animal Pathology, Faculty of Veterinary Sciences, University of Concepcion, Chillan 3787000, ChileDepartment of Internal Medicine, Faculty of Medicine, University of Concepcion, Concepción 4030000, ChileDepartment of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepcion, Concepción 4030000, ChileDepartment of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepcion, Concepción 4030000, ChileDepartment of Pharmacology, Faculty of Biological Sciences, Universidad de Concepción, Concepción 4030000, ChileDepartment of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepcion, Concepción 4030000, ChileVascular Physiology Laboratory, Department of Basic Sciences, Universidad del Bio-Bio, Chillan 3787000, ChileDepartment of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepcion, Concepción 4030000, ChileOxidized 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.https://www.mdpi.com/1422-0067/23/13/7329LOXINLox-1vascular dysfunctionsliver disease |
| spellingShingle | Camila Reyes Estefanía Nova-Lamperti Daniel Duran-Sandoval Daniela Rojas Jorge Gajardo Enrique Guzman-Gutierrez Camila Bustos-Ruiz Valeska Ormazábal Felipe A. Zúñiga Carlos Escudero Claudio Aguayo Loxin Reduced the Inflammatory Response in the Liver and the Aortic Fatty Streak Formation in Mice Fed with a High-Fat Diet International Journal of Molecular Sciences LOXIN Lox-1 vascular dysfunctions liver disease |
| 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 | LOXIN Lox-1 vascular dysfunctions liver disease |
| url | https://www.mdpi.com/1422-0067/23/13/7329 |
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