Kong Qingzan, Liu Miao, Li Yueyan, Zhu Qing, Su Guohai
Department of Cardiology, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Department of Pathology, Blood Center of Shandong Province, Jinan, China.
Ann Palliat Med. 2020 Sep;9(5):3078-3088. doi: 10.21037/apm-20-690.
Evolocumab inhibits the proprotein convertase subtilisin/kexin type 9 protein and is a potent cholesterol-lowering drug. However, the relationship between evolocumab and inflammation, and the effects of evolocumab on the stability of atherosclerotic plaques remain unknown.
Twenty-seven purebred New Zealand rabbits were fed with an atherogenic diet for 2 weeks. The abdominal aortic endothelium was balloon-injured. The rabbits were divided into the atorvastatin (2 mg/kg/day; Ato), evolocumab (7 mg/kg/2 weeks, Evo) and control groups. Intravascular ultrasound (IVUS) images of the abdominal artery were analyzed at 10 and 18 weeks. Additionally, the serum levels of the biomarkers were measured at baseline, and at 10 and 18 weeks.
The serum levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and monocyte chemoattractant protein-1 (MCP-1) increased after 10 weeks of administration of the proatherosclerotic diet, while the levels of high-density lipoprotein cholesterol (HDL-C) and transforming growth factor-β (TGF-β) decreased. The reduction in the serum levels of triglycerides, total cholesterol, LDL-C, MCP-1, TGF-β, and toll-like receptor 4 (TLR4) following treatment with evolocumab was higher than that of atorvastatin. Both evolocumab and atorvastatin reduced the percent atheroma volume. Evolocumab increased the fibrotic% and decreased the necrotic%. Correlation analysis revealed that the levels of triglycerides, total cholesterol, LDL-C, MCP-1, TGF-β, and TLR4 were negatively correlated with the fibrotic%, but were positively correlated with the necrotic%. Multivariate linear regression analysis revealed that treatment with atorvastatin, and especially evolocumab, was a consistent predictor of the percent atheroma volume, and fibrotic and necrotic composition.
Proprotein convertase subtilisin/kexin type 9 regulates the serum levels of lipid and cholesterol may via inflammatory pathways. The results also indicate that evolocumab is more potent than atorvastatin in suppressing the progression and stability of atherosclerotic plaque in rabbits.
依洛尤单抗可抑制前蛋白转化酶枯草溶菌素/克新9型蛋白，是一种强效的降胆固醇药物。然而，依洛尤单抗与炎症之间的关系以及依洛尤单抗对动脉粥样硬化斑块稳定性的影响尚不清楚。
27只纯种新西兰兔喂食致动脉粥样硬化饮食2周。腹主动脉内皮进行球囊损伤。将兔子分为阿托伐他汀组（2毫克/千克/天；阿托）、依洛尤单抗组（7毫克/千克/2周，依沃）和对照组。在第10周和第18周分析腹主动脉的血管内超声（IVUS）图像。此外，在基线以及第10周和第18周测量生物标志物的血清水平。
给予致动脉粥样硬化饮食10周后，甘油三酯、总胆固醇、低密度脂蛋白胆固醇（LDL-C）和单核细胞趋化蛋白-1（MCP-1）的血清水平升高，而高密度脂蛋白胆固醇（HDL-C）和转化生长因子-β（TGF-β）的水平降低。依洛尤单抗治疗后甘油三酯、总胆固醇、LDL-C、MCP-1、TGF-β和Toll样受体4（TLR4）的血清水平降低幅度高于阿托伐他汀。依洛尤单抗和阿托伐他汀均降低了动脉粥样硬化斑块体积百分比。依洛尤单抗增加了纤维化百分比并降低了坏死百分比。相关性分析显示，甘油三酯、总胆固醇、LDL-C、MCP-1、TGF-β和TLR4的水平与纤维化百分比呈负相关，但与坏死百分比呈正相关。多变量线性回归分析显示，阿托伐他汀治疗，尤其是依洛尤单抗治疗，是动脉粥样硬化斑块体积百分比以及纤维化和坏死成分的一致预测指标。
前蛋白转化酶枯草溶菌素/克新9型可能通过炎症途径调节脂质和胆固醇的血清水平。结果还表明，依洛尤单抗在抑制兔动脉粥样硬化斑块进展和稳定性方面比阿托伐他汀更有效。
