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Subcutaneous Administration of Apolipoprotein J-Derived Mimetic Peptide d-[113–122]apoJ Improves LDL and HDL Function and Prevents Atherosclerosis in LDLR-KO Mice
Mimetic peptides are potential therapeutic agents for atherosclerosis. d-[113–122]apolipoprotein (apo) J (d-[113–122]apoJ) is a 10-residue peptide that is predicted to form a class G* amphipathic helix 6 from apoJ; it shows anti-inflammatory and anti-atherogenic properties. In the present study, we...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356811/ https://www.ncbi.nlm.nih.gov/pubmed/32485898 http://dx.doi.org/10.3390/biom10060829 |
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author | Rivas-Urbina, Andrea Rull, Anna Aldana-Ramos, Joile Santos, David Puig, Nuria Farre-Cabrerizo, Nuria Benitez, Sonia Perez, Antonio de Gonzalo-Calvo, David Escola-Gil, Joan Carles Julve, Josep Ordoñez-Llanos, Jordi Sanchez-Quesada, Jose Luis |
author_facet | Rivas-Urbina, Andrea Rull, Anna Aldana-Ramos, Joile Santos, David Puig, Nuria Farre-Cabrerizo, Nuria Benitez, Sonia Perez, Antonio de Gonzalo-Calvo, David Escola-Gil, Joan Carles Julve, Josep Ordoñez-Llanos, Jordi Sanchez-Quesada, Jose Luis |
author_sort | Rivas-Urbina, Andrea |
collection | PubMed |
description | Mimetic peptides are potential therapeutic agents for atherosclerosis. d-[113–122]apolipoprotein (apo) J (d-[113–122]apoJ) is a 10-residue peptide that is predicted to form a class G* amphipathic helix 6 from apoJ; it shows anti-inflammatory and anti-atherogenic properties. In the present study, we analyzed the effect of d-[113–122]apoJ in low-density lipoprotein receptor knockout mice(LDLR-KO) on the development of atherosclerosis and lipoprotein function. Fifteen-week-old female LDLR-KO mice fed an atherogenic Western-type diet were treated for eight weeks with d-[113–122]apoJ peptide, a scrambled peptide, or vehicle. Peptides were administered subcutaneously three days per week (200 µg in 100 µL of saline). After euthanasia, blood and hearts were collected and the aortic arch was analyzed for the presence of atherosclerotic lesions. Lipoproteins were isolated and their composition and functionality were studied. The extent of atherosclerotic lesions was 43% lower with d-[113–122]apoJ treatment than with the vehicle or scramble. The lipid profile was similar between groups, but the high-density lipoprotein (HDL) of d-[113–122]apoJ-treated mice had a higher antioxidant capacity and increased ability to promote cholesterol efflux than the control group. In addition, low-density lipoprotein (LDL) from d-[113–122]apoJ-treated mice was more resistant to induced aggregation and presented lower electronegativity than in mice treated with d-[113–122]apoJ. Our results demonstrate that the d-[113–122]apoJ peptide prevents the extent of atherosclerotic lesions, which could be partially explained by the improvement of lipoprotein functionality. |
format | Online Article Text |
id | pubmed-7356811 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-73568112020-07-22 Subcutaneous Administration of Apolipoprotein J-Derived Mimetic Peptide d-[113–122]apoJ Improves LDL and HDL Function and Prevents Atherosclerosis in LDLR-KO Mice Rivas-Urbina, Andrea Rull, Anna Aldana-Ramos, Joile Santos, David Puig, Nuria Farre-Cabrerizo, Nuria Benitez, Sonia Perez, Antonio de Gonzalo-Calvo, David Escola-Gil, Joan Carles Julve, Josep Ordoñez-Llanos, Jordi Sanchez-Quesada, Jose Luis Biomolecules Article Mimetic peptides are potential therapeutic agents for atherosclerosis. d-[113–122]apolipoprotein (apo) J (d-[113–122]apoJ) is a 10-residue peptide that is predicted to form a class G* amphipathic helix 6 from apoJ; it shows anti-inflammatory and anti-atherogenic properties. In the present study, we analyzed the effect of d-[113–122]apoJ in low-density lipoprotein receptor knockout mice(LDLR-KO) on the development of atherosclerosis and lipoprotein function. Fifteen-week-old female LDLR-KO mice fed an atherogenic Western-type diet were treated for eight weeks with d-[113–122]apoJ peptide, a scrambled peptide, or vehicle. Peptides were administered subcutaneously three days per week (200 µg in 100 µL of saline). After euthanasia, blood and hearts were collected and the aortic arch was analyzed for the presence of atherosclerotic lesions. Lipoproteins were isolated and their composition and functionality were studied. The extent of atherosclerotic lesions was 43% lower with d-[113–122]apoJ treatment than with the vehicle or scramble. The lipid profile was similar between groups, but the high-density lipoprotein (HDL) of d-[113–122]apoJ-treated mice had a higher antioxidant capacity and increased ability to promote cholesterol efflux than the control group. In addition, low-density lipoprotein (LDL) from d-[113–122]apoJ-treated mice was more resistant to induced aggregation and presented lower electronegativity than in mice treated with d-[113–122]apoJ. Our results demonstrate that the d-[113–122]apoJ peptide prevents the extent of atherosclerotic lesions, which could be partially explained by the improvement of lipoprotein functionality. MDPI 2020-05-29 /pmc/articles/PMC7356811/ /pubmed/32485898 http://dx.doi.org/10.3390/biom10060829 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Rivas-Urbina, Andrea Rull, Anna Aldana-Ramos, Joile Santos, David Puig, Nuria Farre-Cabrerizo, Nuria Benitez, Sonia Perez, Antonio de Gonzalo-Calvo, David Escola-Gil, Joan Carles Julve, Josep Ordoñez-Llanos, Jordi Sanchez-Quesada, Jose Luis Subcutaneous Administration of Apolipoprotein J-Derived Mimetic Peptide d-[113–122]apoJ Improves LDL and HDL Function and Prevents Atherosclerosis in LDLR-KO Mice |
title | Subcutaneous Administration of Apolipoprotein J-Derived Mimetic Peptide d-[113–122]apoJ Improves LDL and HDL Function and Prevents Atherosclerosis in LDLR-KO Mice |
title_full | Subcutaneous Administration of Apolipoprotein J-Derived Mimetic Peptide d-[113–122]apoJ Improves LDL and HDL Function and Prevents Atherosclerosis in LDLR-KO Mice |
title_fullStr | Subcutaneous Administration of Apolipoprotein J-Derived Mimetic Peptide d-[113–122]apoJ Improves LDL and HDL Function and Prevents Atherosclerosis in LDLR-KO Mice |
title_full_unstemmed | Subcutaneous Administration of Apolipoprotein J-Derived Mimetic Peptide d-[113–122]apoJ Improves LDL and HDL Function and Prevents Atherosclerosis in LDLR-KO Mice |
title_short | Subcutaneous Administration of Apolipoprotein J-Derived Mimetic Peptide d-[113–122]apoJ Improves LDL and HDL Function and Prevents Atherosclerosis in LDLR-KO Mice |
title_sort | subcutaneous administration of apolipoprotein j-derived mimetic peptide d-[113–122]apoj improves ldl and hdl function and prevents atherosclerosis in ldlr-ko mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356811/ https://www.ncbi.nlm.nih.gov/pubmed/32485898 http://dx.doi.org/10.3390/biom10060829 |
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