Reducing the Damage of Ox-LDL/LOX-1 Pathway to Vascular Endothelial Barrier Can Inhibit Atherosclerosis.
Reducing the Damage of Ox-LDL/LOX-1 Pathway to Vascular Endothelial Barrier Can Inhibit Atherosclerosis.
复制标题
减少Ox-LDL/LOX-1通路对血管内皮屏障的损伤可抑制动脉粥样硬化
DOI：
10.1155/2022/7541411
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发表时间：
2022
影响因子：
--
通讯作者：
Wei Y
中科院分区：
文献类型：
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作者：
Guo X;Guo Y;Wang Z;Cao B;Zheng C;Zeng Z;Wei Y
目的氧化低密度脂蛋白（Ox-LDL）介导的血管内皮屏障破坏是动脉粥样硬化形成的起始环节。本研究旨在探讨Ox-ApoB多肽片段（Ox-ApoB-PF）的免疫干预能否通过LOX-1受体阻断Ox-LDL在血管内皮细胞的沉积，从而保护血管内皮细胞的屏障功能和存活状态，抑制动脉粥样硬化的进展。方法与结果为明确Ox-LDL对血管内皮细胞的损伤及Ox-ApoB-PF免疫干预的保护作用，我们进行了一系列相应的体内外实验。体外实验结果表明，Ox-LDL可激活内皮细胞凋亡途径，降低内皮连接蛋白的表达，影响其迁移、变形和形成能力，最终破坏血管内皮屏障功能。内皮细胞通透性的增加导致内皮层下巨噬细胞对Ox-LDL的吞噬作用急剧增加。同时，Ox-LDL刺激诱导内皮细胞LOX-1表达显著上调，并增加内皮细胞趋化因子和粘附因子的表达。Ox-ApoB-PF抗体可显著降低上述有害作用。体内实验结果表明，Ox-ApoB-PF主动免疫干预可保护内皮屏障功能，减少斑块内巨噬细胞沉积和炎症反应，减轻斑块内脂质沉积、凋亡和坏死，增强肝脏巨噬细胞清除Ox-LDL的能力。最终，斑块的进展和斑块中坏死核心的形成可以被抑制。结论抗Ox-ApoB-PF抗体可能通过阻断Ox-LDL/LOX-1在血管内皮细胞上的结合而保护内皮细胞的生理功能和存活状态。Ox-ApoB-PF免疫干预通过保护血管内皮屏障功能抑制动脉粥样硬化病变的发生和发展。
Aim The destruction of the vascular endothelial barrier mediated by Ox-LDL is the initial link to atherosclerosis. Here, we aimed to determine whether the immunological intervention with Ox-ApoB polypeptide fragment (Ox-ApoB-PF) can block the deposition of Ox-LDL in vascular endothelial cells through LOX-1 receptors, thereby protecting the barrier function and survival status of vascular endothelial cells and inhibiting the progression of atherosclerosis. Methods and Results In order to determine the harm of Ox-LDL to vascular endothelial cells and the protective effect of immune intervention with Ox-ApoB-PF, we conducted a series of corresponding experiments in vitro and in vivo. The in vitro results showed that Ox-LDL can activate endothelial cell apoptosis pathway; reduce the expression of endothelial junction proteins; affect the migration, deformation, and forming ability; and ultimately destroy the vascular endothelial barrier function. The increased permeability of endothelial cells led to a sharp increase in the phagocytosis of Ox-LDL by macrophages under the endothelial layer. Meanwhile, Ox-LDL stimulation induced a significant upregulation of LOX-1 in endothelial cells and increased the expression of endothelial cell chemokines and adhesion factors. Ox-ApoB-PF antibodies can significantly reduce the abovementioned harmful effects. The in vivo results showed that active immune intervention through Ox-ApoB-PF can protect the endothelial barrier function; reduce macrophage deposition and the inflammatory response in plaques; alleviate lipid deposition in the plaques, as well as apoptosis and necrosis; and increase the ability of liver macrophages to clear Ox-LDL. Eventually, the progression of plaque and the formation of necrotic cores in plaques can be inhibited. Conclusions An Ox-ApoB-PF antibody may protect the endothelial cell physiological function and survival status by blocking the combination of Ox-LDL/LOX-1 in vascular endothelial cells. Immune intervention with Ox-ApoB-PF inhibits the occurrence and development of atherosclerotic lesions by protecting the vascular endothelial barrier function.