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COL6A6 肽疫苗通过诱导免疫应答和调节脂质代谢缓解小鼠动脉粥样硬化

COL6A6 Peptide Vaccine Alleviates Atherosclerosis through Inducing Immune Response and Regulating Lipid Metabolism in Mice.

机构信息

Department of Pathophysiology, Key Lab for Shock and Microcirculation Research of Guangdong, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.

出版信息

Cells. 2024 Sep 21;13(18):1589. doi: 10.3390/cells13181589.

Abstract

Atherosclerosis is an autoimmune disease characterized by lipid imbalances and chronic inflammation within blood vessels, with limited preventive and treatment options currently available. In this study, a vaccine prepared with COL6A6 peptide (named the Pep_A6 vaccine) was administered to immunize mice, and the immune mechanism of the Pep_A6 vaccine against atherosclerosis was first investigated. The results of arterial oil red O staining demonstrated that the Pep_A6 vaccine significantly reduced the atherosclerotic plaque area in mice fed with a high-fat diet for 20 weeks. A flow cytometry analysis revealed that the Pep_A6 vaccine inhibited Th1 cell differentiation and increased the proportion of Treg cells. Furthermore, there was a significant increase in Ly6C monocytes observed in the vaccinated group. The ELISA results showed that the Pep_A6 vaccine induced a significant expression of Pep_A6-specific antibody IgG and IgG1 in mouse serum. Additionally, we found that the Pep_A6 vaccine significantly decreased serum LDL-C content and regulated the expression of genes related to liver lipid metabolism. Together, our findings suggest that the Pep_A6 vaccine alleviates atherosclerosis by inducing a positive immune response and regulating lipid metabolism, providing new insights into potential prevention strategies for atherosclerosis as an innovative vaccine.

摘要

动脉粥样硬化是一种自身免疫性疾病,其特征是血管内脂质失衡和慢性炎症,目前可预防和治疗的选择有限。在这项研究中,用 COL6A6 肽制备的疫苗(称为 Pep_A6 疫苗)被用于免疫小鼠,首次研究了 Pep_A6 疫苗对动脉粥样硬化的免疫机制。动脉油红 O 染色的结果表明,Pep_A6 疫苗显著减少了高脂饮食喂养 20 周的小鼠的动脉粥样硬化斑块面积。流式细胞术分析显示,Pep_A6 疫苗抑制了 Th1 细胞分化,增加了 Treg 细胞的比例。此外,在接种疫苗的组中观察到 Ly6C 单核细胞显著增加。ELISA 结果表明,Pep_A6 疫苗诱导了小鼠血清中 Pep_A6 特异性抗体 IgG 和 IgG1 的显著表达。此外,我们发现 Pep_A6 疫苗显著降低了血清 LDL-C 含量,并调节了与肝脏脂质代谢相关的基因的表达。总之,我们的研究结果表明,Pep_A6 疫苗通过诱导积极的免疫反应和调节脂质代谢来缓解动脉粥样硬化,为动脉粥样硬化的潜在预防策略提供了新的思路,作为一种创新疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bf3/11429512/a6d4c36db406/cells-13-01589-g001a.jpg

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