Ou Lingling, Li Xin, Chen Baihong, Ge Zhenhuang, Zhang Junyi, Zhang Ye, Cai Gaotai, Li Zhen, Wang Ping, Dong Wenqi
1 The First Affiliated Hospital of Jinan University, Guangzhou, China.
2 School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China.
J Cardiovasc Pharmacol Ther. 2018 Mar;23(2):162-173. doi: 10.1177/1074248417724870. Epub 2017 Sep 27.
Atherosclerosis is a chronic inflammatory vascular disease characterized by lipid accumulation and endothelial dysfunction. Cytoglobin has been shown to exert protective effects under oxidative stress conditions. The aim of this study was to determine whether recombinant human cytoglobin (rhCYGB) has protective effects against atherosclerosis. We intraperitoneally injected rhCYGB (0, 4, or 7 mg/kg BW) into the atherosclerotic rats daily for 60 days. The rhCYGB injections reduced low-density lipoprotein cholesterol (LDL-C) levels and increased high-density lipoprotein cholesterol levels in a dose-dependent manner, rhCYGB (7 mg/kg) significantly attenuated atherosclerosis. Blood proteins were separated by 2-dimensional electrophoresis and analyzed by mass spectrometry, and the majority of the proteins in question were participated in oxidative stress pathways and cardiovascular diseases. Human hepatocellular liver carcinoma cell line (HepG2) cells were treated with oleic acid (0.3 mmol/L), and Human acute monocytic leukemia cell line (THP-1) cells were incubated with oxidized LDL (ox-LDL; 50 µg/mL) to induce foam cell (FC) formation in vitro. Treatment with different concentrations of rhCYGB (0, 5, 10, and 15 μg/mL) significantly decreased the lipid droplet levels in HepG2 cells and cholesterol ester levels in FCs. Moreover, rhCYGB significantly increased superoxide dismutase and glutathione peroxidase activity and decreased malondialdehyde and nicotinamide adenine dinucleotide phosphate oxidase activity in cells. In addition, rhCYGB decreased NO and Reactive oxygen species (ROS) levels in FCs by functioning as an NO dioxygenase enzyme and ROS scavenger. Taken together, our findings indicate that rhCYGB prevented atherosclerosis by regulating lipid metabolism and oxidative stress. Our study provides insights into the possible usefulness of rhCYGB as an antiatherosclerosis agent.
动脉粥样硬化是一种以脂质积聚和内皮功能障碍为特征的慢性炎症性血管疾病。细胞珠蛋白已被证明在氧化应激条件下发挥保护作用。本研究的目的是确定重组人细胞珠蛋白（rhCYGB）是否对动脉粥样硬化具有保护作用。我们每天向动脉粥样硬化大鼠腹腔注射rhCYGB（0、4或7mg/kg体重），持续60天。rhCYGB注射以剂量依赖的方式降低了低密度脂蛋白胆固醇（LDL-C）水平并提高了高密度脂蛋白胆固醇水平，rhCYGB（7mg/kg）显著减轻了动脉粥样硬化。通过二维电泳分离血液蛋白质并进行质谱分析，大多数相关蛋白质参与氧化应激途径和心血管疾病。用人油酸（0.3mmol/L）处理人肝癌细胞系（HepG2）细胞，并用氧化低密度脂蛋白（ox-LDL；50μg/mL）孵育人急性单核细胞白血病细胞系（THP-1）细胞以在体外诱导泡沫细胞（FC）形成。用不同浓度的rhCYGB（0、5、10和15μg/mL）处理显著降低了HepG2细胞中的脂滴水平和FC中的胆固醇酯水平。此外，rhCYGB显著提高了细胞中超氧化物歧化酶和谷胱甘肽过氧化物酶的活性，并降低了丙二醛和烟酰胺腺嘌呤二核苷酸磷酸氧化酶的活性。此外，rhCYGB通过作为一种一氧化氮双加氧酶和活性氧清除剂来降低FC中的一氧化氮和活性氧水平。综上所述，我们的研究结果表明rhCYGB通过调节脂质代谢和氧化应激来预防动脉粥样硬化。我们的研究为rhCYGB作为抗动脉粥样硬化药物的潜在用途提供了见解。
