Endothelial cell (EC) migration is essential for healing vascular injuries. Previous studies suggest that high-density lipoprotein (HDL) and apolipoprotein A-I (apoA-I), the major protein constituent of HDL, have endothelial healing functions. In cardiovascular disease, HDL is modified by myeloperoxidase (MPO) and N -homocysteine, resulting in apoA-I/apoA-II heterodimer and N -homocysteinylated ( N -Hcy) apoA-I formation. This study investigated whether these modifications attenuate HDL-mediated endothelial healing. Wound healing assays were performed to analyze the effect of MPO-oxidized HDL and N -Hcy HDL in vitro . HDL obtained from patients with varying troponin I levels were also examined. MPO-oxidized HDL reduces EC migration compared to normal HDL in vitro , and N -Hcy HDL showed a decreasing trend toward EC migration. EC migration after treatment with HDL from patients was decreased compared to HDL isolated from healthy controls. Increased apoA-I/apoA-II heterodimer and N -Hcy apoA-I levels were also detected in HDL from patients. Wound healing cell migration was significantly negatively correlated with the ratio of apoA-I/apoA-II heterodimer to total apoA-II and N -Hcy apoA-I to total apoA-I. MPO-oxidized HDL containing apoA-I/apoA-II heterodimers had a weaker endothelial healing function than did normal HDL. These results indicate that MPO-oxidized HDL and N -Hcy HDL play a key role in the pathogenesis of cardiovascular disease.

中文翻译：

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髓过氧化物酶氧化和高密度脂蛋白N-同型半胱氨酸化对内皮修复功能的影响

内皮细胞 (EC) 迁移对于愈合血管损伤至关重要。先前的研究表明，高密度脂蛋白 (HDL) 和载脂蛋白 AI (apoA-I) 是 HDL 的主要蛋白质成分，具有内皮愈合功能。在心血管疾病中，HDL 被髓过氧化物酶 (MPO) 和 N-同型半胱氨酸修饰，导致 apoA-I/apoA-II 异二聚体和 N-同型半胱氨酸化 (N-Hcy) apoA-I 形成。本研究调查了这些修饰是否会减弱 HDL 介导的内皮愈合。进行伤口愈合试验以分析 MPO 氧化 HDL 和 N-Hcy HDL 在体外的作用。还检查了从具有不同肌钙蛋白 I 水平的患者获得的 HDL。与体外正常 HDL 相比，MPO 氧化的 HDL 减少了 EC 迁移，并且 N-Hcy HDL 显示出 EC 迁移减少的趋势。与从健康对照分离的 HDL 相比，来自患者的 HDL 治疗后 EC 迁移减少。在患者的 HDL 中也检测到增加的 apoA-I/apoA-II 异二聚体和 N-Hcy apoA-I 水平。伤口愈合细胞迁移与 apoA-I/apoA-II 异二聚体与总 apoA-II 的比率和 N-Hcy apoA-I 与总 apoA-I 的比率呈显着负相关。含有 apoA-I/apoA-II 异二聚体的 MPO 氧化 HDL 具有比正常 HDL 更弱的内皮愈合功能。这些结果表明，MPO氧化的HDL和N-Hcy HDL在心血管疾病的发病机制中起关键作用。伤口愈合细胞迁移与 apoA-I/apoA-II 异二聚体与总 apoA-II 的比率和 N-Hcy apoA-I 与总 apoA-I 的比率呈显着负相关。含有 apoA-I/apoA-II 异二聚体的 MPO 氧化 HDL 具有比正常 HDL 更弱的内皮愈合功能。这些结果表明，MPO氧化的HDL和N-Hcy HDL在心血管疾病的发病机制中起关键作用。伤口愈合细胞迁移与 apoA-I/apoA-II 异二聚体与总 apoA-II 的比率和 N-Hcy apoA-I 与总 apoA-I 的比率呈显着负相关。含有 apoA-I/apoA-II 异二聚体的 MPO 氧化 HDL 具有比正常 HDL 更弱的内皮愈合功能。这些结果表明，MPO氧化的HDL和N-Hcy HDL在心血管疾病的发病机制中起关键作用。