Home > Articles > Published articles > Subcutaneous Administration of Apolipoprotein J-Derived Mimetic Peptide -[113-122]apoJ Improves LDL and HDL Function and Prevents Atherosclerosis in LDLR-KO Mice |
Date: | 2020 |
Abstract: | Mimetic peptides are potential therapeutic agents for atherosclerosis. -[113-122]apolipoprotein (apo) J (-[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 -[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 -[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 -[113-122]apoJ treatment than with the vehicle or scramble. The lipid profile was similar between groups, but the high-density lipoprotein (HDL) of -[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 -[113-122]apoJ-treated mice was more resistant to induced aggregation and presented lower electronegativity than in mice treated with -[113-122]apoJ. Our results demonstrate that the -[113-122]apoJ peptide prevents the extent of atherosclerotic lesions, which could be partially explained by the improvement of lipoprotein functionality. |
Grants: | Ministerio de Economía y Competitividad PI13/00364 Ministerio de Economía y Competitividad PI16/00471 Instituto de Salud Carlos III PI17-00232 Ministerio de Economía y Competitividad PI16-00139 Ministerio de Ciencia e Innovación CB07/06/2008 Instituto de Salud Carlos III CB07/08/0016 Instituto de Salud Carlos III FI17/00031 Ministerio de Economía y Competitividad CD12-00439 Instituto de Salud Carlos III CP19/00146 Instituto de Salud Carlos III CPII18/00004 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-1149 |
Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
Language: | Anglès |
Document: | Article ; recerca ; Versió publicada |
Subject: | Mimetic peptide ; Atherosclerosis ; Lipoprotein function ; Apolipoprotein J ; LDL ; HDL ; Mice |
Published in: | Biomolecules, Vol. 10, Issue 6 (May 2020) , art. 829, ISSN 2218-273X |
19 p, 3.0 MB |