Low-density lipoprotein aggregation is inhibited by apolipoprotein J-derived mimetic peptide D-[113–122]apoJ

Rivas-Urbina, Andrea; Rull, Anna; Montoliu‐Gaya, Laia; Pérez-Cuellar, Montserrat; Ordóñez-Llanos, Jordi; Villegas, Sandra; Sánchez-Quesada, José Luís

doi:10.1016/j.bbalip.2019.158541

Cited by 10 publications

(11 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Based on previous studies, we hypothesized that the peptide d -[113–122]apoJ could accomplish protective actions by improving both HDL and LDL function. On one hand, the d -[113–122]apoJ mimetic peptide has in vitro protective effects on human LDL aggregation, a crucial LDL event for the development of atherosclerosis [ 22 ]. On the other hand, this peptide was proven to retard atherosclerosis in apoE KO mice by improving the anti-inflammatory properties and the cholesterol efflux capacity of HDL [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, the specific mechanisms by which the peptide exerts this protective action are not well understood. Regarding LDL, we previously reported that d -[113–122]apoJ protects LDL from in vitro aggregation induced by different mechanisms, including spontaneous and SMase-induced aggregation [ 22 ]. We proposed that this effect was mediated by the binding of the peptide to hydrophobic patches in the lipoprotein surface generated during the aggregation process, avoiding the interaction of different LDL particles.…”

Section: Discussionmentioning

confidence: 99%

“…This peptide is a 10-residue peptide spanning the predicted class G* amphipathic helix 6 from apoJ and has been successfully used to retard atherosclerosis in apoE-knockout mice, which was attributed to its capacity to improve the anti-inflammatory properties of HDL [13]. Our group previously described that both the whole molecule of apoJ [21] and the peptide d- [113][114][115][116][117][118][119][120][121][122]apoJ [22] inhibit SMase-induced and spontaneous LDL aggregation in vitro. Based on these observations, the aim of the present study was to analyze the effect of the d- [113][114][115][116][117][118][119][120][121][122]apoJ peptide on lipoprotein function and the development of atherosclerosis.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2020

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Notably, the 4F peptide has been shown to reduce experimental murine atherosclerosis, especially when applied during the early stages of atherosclerosis [106][107][108]. Recently, Rivas-Urbina et al showed in LDL receptor-deficient mice that a 10-residue peptide from apoJ (clusterin) inhibits LDL aggregation by binding to modified LDL particles and that it also reduces atherosclerosis [109,110]. Thus, the LDL surface lipid monolayer-stabilizing effect of amphipathic peptides appears not to depend on the amino acid structure of the peptide, but rather on its ability to bind to the surface lipid monolayer.…”

Section: Figurementioning

confidence: 99%

Aggregation Susceptibility of Low-Density Lipoproteins—A Novel Modifiable Biomarker of Cardiovascular Risk

Öörni

Kovanen

2021

JCM

View full text Add to dashboard Cite

Circulating low-density lipoprotein (LDL) particles enter the arterial intima where they bind to the extracellular matrix and become modified by lipases, proteases, and oxidizing enzymes and agents. The modified LDL particles aggregate and fuse into larger matrix-bound lipid droplets and, upon generation of unesterified cholesterol, cholesterol crystals are also formed. Uptake of the aggregated/fused particles and cholesterol crystals by macrophages and smooth muscle cells induces their inflammatory activation and conversion into foam cells. In this review, we summarize the causes and consequences of LDL aggregation and describe the development and applications of an assay capable of determining the susceptibility of isolated LDL particles to aggregate when exposed to human recombinant sphingomyelinase enzyme ex vivo. Significant person-to-person differences in the aggregation susceptibility of LDL particles were observed, and such individual differences largely depended on particle lipid composition. The presence of aggregation-prone LDL in the circulation predicted future cardiovascular events in patients with atherosclerotic cardiovascular disease. We also discuss means capable of reducing LDL particles’ aggregation susceptibility that could potentially inhibit LDL aggregation in the arterial wall. Whether reductions in LDL aggregation susceptibility are associated with attenuated atherogenesis and a reduced risk of atherosclerotic cardiovascular diseases remains to be studied.

show abstract

“…Among them, the active peptides correspond to 113-122 residues, which were synthesized as D-amino acids [31]. D-(113-122) ApoJ, a 10-residue peptide spanning the predicted class G amphipathic helix 6 from ApoJ, prevented SMase-induced LDL aggregation through its ability to bind to hydrophobic regions of LDL particle surface prone to LDL aggregation [52,53].…”

Section: Apoj-based Peptidesmentioning

confidence: 99%

Apolipoprotein and LRP1-Based Peptides as New Therapeutic Tools in Atherosclerosis

Amaro

Curco²,

García

et al. 2021

JCM

View full text Add to dashboard Cite

Apolipoprotein (Apo)-based mimetic peptides have been shown to reduce atherosclerosis. Most of the ApoC-II and ApoE mimetics exert anti-atherosclerotic effects by improving lipid profile. ApoC-II mimetics reverse hypertriglyceridemia and ApoE-based peptides such as Ac-hE18A-NH2 reduce cholesterol and triglyceride (TG) levels in humans. Conversely, other classes of ApoE and ApoA-I mimetic peptides and, more recently, ApoJ and LRP1-based peptides, exhibit several anti-atherosclerotic actions in experimental models without influencing lipoprotein profile. These other mimetic peptides display at least one atheroprotective mechanism such as providing LDL stability against mechanical modification or conferring protection against the action of lipolytic enzymes inducing LDL aggregation in the arterial intima. Other anti-atherosclerotic effects exerted by these peptides also include protection against foam cell formation and inflammation, and induction of reverse cholesterol transport. Although the underlying mechanisms of action are still poorly described, the recent findings suggest that these mimetics could confer atheroprotection by favorably influencing lipoprotein function rather than lipoprotein levels. Despite the promising results obtained with peptide mimetics, the assessment of their stability, atheroprotective efficacy and tissue targeted delivery are issues currently under progress.

show abstract

Low-density lipoprotein aggregation is inhibited by apolipoprotein J-derived mimetic peptide D-[113–122]apoJ

Cited by 10 publications

References 45 publications

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

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

Aggregation Susceptibility of Low-Density Lipoproteins—A Novel Modifiable Biomarker of Cardiovascular Risk

Apolipoprotein and LRP1-Based Peptides as New Therapeutic Tools in Atherosclerosis

Contact Info

Product

Resources

About