Copyright (c) 2023 Bo Zhang, Weichang Xia, Jingqun Zhou, Jianfeng Lv, Qiuting Dai, Xiangyan Li, Qinqin Tian, Xijian Liu, Xuan Du, Rong Tu, Shouyi Liu
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
The undersigned hereby assign all rights, included but not limited to copyright, for this manuscript to CMB Association upon its submission for consideration to publication on Cellular and Molecular Biology. The rights assigned include, but are not limited to, the sole and exclusive rights to license, sell, subsequently assign, derive, distribute, display and reproduce this manuscript, in whole or in part, in any format, electronic or otherwise, including those in existence at the time this agreement was signed. The authors hereby warrant that they have not granted or assigned, and shall not grant or assign, the aforementioned rights to any other person, firm, organization, or other entity. All rights are automatically restored to authors if this manuscript is not accepted for publication.Oxidized low-density lipoprotein induces M2-type differentiation of macrophages to promote the protracted progression of atherosclerotic inflammation in high-fat diet-fed ApoE -/- mice
Corresponding Author(s) : Jingqun Zhou
Cellular and Molecular Biology,
Vol. 69 No. 15: New discoveries in inflammatory factors
Abstract
In this study, the significance of oxidized low-density lipoprotein (ox-LDL) in promoting the progression of atherosclerosis was investigated by inducing the differentiation of macrophages into the M2 subtype within a high-fat diet-induced ApoE -/- mouse model. The study also evaluated the effects of β2-AR agonists and blockers on this process. Ox-LDL was found to have significantly promoted the differentiation of macrophages into the M2 type and induced related functional alterations. Furthermore, it activated the pyroptosis pathway and encouraged the release of lactate dehydrogenase. The administration of β2-AR agonists intensified these processes, while β2-AR blockers had the opposite effect. In animal experiments, the model group displayed elevated numbers of M2-type macrophages beneath the aortic root intima, an increased rate of plaque destruction, and the formation of atherosclerotic plaques compared to the control group. The SAL (Salbutamol) group exhibited even more severe plaque development than the model group. Conversely, the ICI (ICI118551) group demonstrated M2-type macrophage levels comparable to the control group, with a higher plaque destruction rate than controls but significantly lower than the model group, and no atherosclerotic plaques. These findings suggest that ox-LDL promoted the differentiation of recruited monocytes into M2-type macrophages, leading to a shift in the inflammatory response from M1 to M2 macrophages. This alteration resulted in the persistence of atherosclerotic inflammation, as M2-type macrophages were prone to cell membrane rupture (such as pyroptosis), contributing to the continuous recruitment of circulating monocytes and heightened inflammatory reactions within atherosclerotic plaques. Consequently, this process fueled the progression of atherosclerosis.
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