scholarly journals Subcutaneous Administration of Apolipoprotein J-Derived Mimetic Peptide d-[113–122]apoJ Improves LDL and HDL Function and Prevents Atherosclerosis in LDLR-KO Mice

Biomolecules ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 829 ◽  
Author(s):  
Andrea Rivas-Urbina ◽  
Anna Rull ◽  
Joile Aldana-Ramos ◽  
David Santos ◽  
Nuria Puig ◽  
...  

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.

Circulation ◽  
1999 ◽  
Vol 99 (24) ◽  
pp. 3110-3117 ◽  
Author(s):  
Hiroharu Kataoka ◽  
Noriaki Kume ◽  
Susumu Miyamoto ◽  
Manabu Minami ◽  
Hideaki Moriwaki ◽  
...  

Author(s):  
Ramandeep Kaur ◽  
Kabo Masisi ◽  
Mahboubeh Molaei ◽  
Khoung Le ◽  
Gabor Fischer ◽  
...  

Kgengwe fruits are commonly consumed in Sub-Saharan countries. Recent reports indicated low coronary artery disease rates in those regions. To investigate anti atherogenic properties and potential mechanisms of action of Kgengwe seed powder (KSP), male low-density lipoprotein receptor knockout (LDL-r-KO) mice were fed with an atherogenic diet supplemented with (treated, n=10) or without (controls, n=10) 10% (w/w) KSP for 20 weeks. Proximate analysis revealed that KSP contained 38% fiber and 15% lipids. KSP supplementation was not associated with significant changes in body weight gain rate, food intake, and plasma lipid levels. However, the average atherosclerotic lesion size in the aortic roots in the KSP-treated group was 58% smaller than that in the control group (0.26 vs 0.11 mm2, p<0.05). This strong anti-atherogenic effect was associated with significant increases in the average plasma levels of certain cytokines such as IL-10 (6 vs 13, pg/mL, p<0.05), GM-CSF (0.1 vs 0.2, pg/mL, p<0.05), and EPO (7 vs 16, pg/mL, p<0.05) along with reductions in the average levels of plasma MCP-1 (19 vs 14, pg/mL, p<0.05) and MIP-2 (28 vs 13, pg/mL, p<0.05). Except for relatively high levels of saturated fatty acids, KSP possesses balanced nutrient compositions with strong anti-atherogenic properties which may be mediated through alterations in inflammatory pathways. Additional studies warrant confirmation and mechanism(s) of action of such effects. Novelty bullets 1. Kgengwe seeds prevent atherogenesis in LDL-r-KO mice 2. Kgengwe seeds increase circulating levels of IL-10 and EPO 3. No reduction in plasma total cholesterol levels


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