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- W4312634562 abstract "Background: The use of nanoparticles for efficient delivery of therapeutic modalities in humans is rapidly increasing. We have previously reported that a nanovaccine consisting of apoB-100 peptide P210 complexed with amphiphilic micelles (P210-PAM) significantly reduces atherosclerosis in apoE-/- mice. In this study, we defined the mechanistic pathway for the atheroprotective effect of P210-PAM. Methods and Results: Seven-week male apoE-/- mice were immunized with P210-PAM or mouse serum albumin peptide amphiphile micelles (MSA-PAM) at a dose of 100ug per injection at 7, 10, and 12 weeks of age. One week after the second booster, mice were euthanized and the splenocytes were collected for immune profiling and immune assays. A second group of immunized mice were injected with thioglycolate to elicit peritoneal macrophages. Splenocytes from P210-PAM mice collected 1 week after the second booster had significantly increased CD4+CD25+FoxP3+ Treg cells and CD8+CTLA-4+ T cells compared to MSA-PAM mice (N=9 each; P≤0.05). Splenocytes from P210-PAM mice had reduced CD4+ T cell proliferation and CD8+CD107a+ T cells in response to P210 recall compared to MSA-PAM (N=8 and 9, respectively; P<0.05). No effects were observed with non-specific PMA/ionomycin stimulation indicating antigen-specificity. Splenic mRNA expression of IL-1β was unchanged but there was significant reduction in IL-1R1, IL-6, and IL-17a in P210-PAM mice (N=12 each; P<0.05). Flow cytometric analysis indicated that the reduced IL-1R1 expression was specific to F4/80+ macrophages (N=10 each; P<0.05). Macrophages enriched from the peritoneal exudate showed significantly reduced iNOS, IL-6, IL-12 and IL-10 mRNA expression in P210-PAM mice compared to MSA-PAM (N=4 each; P<0.05). Conclusion: The mechanism of the protective effect of P210-PAM nanoparticles in reducing the immune-inflammatory response in atherosclerosis is at the level of both adaptive T cell response as well as innate macrophage response. The use of P210-PAM in future investigations as potential clinical therapy for atherosclerosis is thus warranted." @default.
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- W4312634562 date "2022-05-01" @default.
- W4312634562 modified "2023-10-18" @default.
- W4312634562 title "Abstract 510: Immune-regulatory Mechanism Of P210-complexed Nanoparticle Immunization For Atherosclerosis" @default.
- W4312634562 doi "https://doi.org/10.1161/atvb.42.suppl_1.510" @default.
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