Department of Pharmacology and Therapeutics, College of Medicine, University of Kufa, Najaf, Iraq.
Department of Pharmacology, College of Medicine, University of Basra, Basra, Iraq.
J Med Life. 2023 May;16(5):759-765. doi: 10.25122/jml-2021-0210.
Evolocumab, a PCSK-9 inhibitor, is known for its ability to reduce low-density lipoprotein cholesterol (LDL-C). This study aimed to investigate the effects of evolocumab, alone or in combination with atorvastatin, on the progression of atherosclerosis. Fifty male domestic rabbits were randomly assigned to five groups: control, high cholesterol diet, evolocumab vehicle (dimethyl sulfoxide, DMSO), evolocumab alone, and evolocumab plus atorvastatin. Serum levels of interleukin 10 (IL-10), IL-17, IL-1β, intracellular adhesion molecule (ICAM), and vascular adhesion molecule (VCAM) were measured. Toll-like receptor (TLR) expression on monocytes was evaluated using flow cytometry. Histopathological examination and measurement of intimal thickness (IT) were also conducted. The results revealed that the evolocumab produced a statistically significant (p<0.05) reduction in lipid profile at 5 weeks, with the peak effect occurring at 10 weeks. Furthermore, the inhibitor reduced TLRs at 10 weeks to 10.83±1.8 and intimal thickness to 160.66±9.45. IL-17, IL-1β, ICAM, and VCAM were significantly reduced by evolocumab treatment, with the improvement of the histopathological changes in the aortic wall. The combination of evolocumab and atorvastatin caused a more statistically significant reduction in TLRs at 10 weeks to 5.08±1.2 and intimal thickness to 121.79±5.3. IL-17, IL-1β, ICAM, and VCAM were significantly (p<0.05) reduced by the combination, and the histopathological changes in the aortic wall were significantly improved. In conclusion, evolocumab delays the progression of atherosclerosis by modulating inflammatory pathways.
依洛尤单抗，一种 PCSK-9 抑制剂，以降低低密度脂蛋白胆固醇（LDL-C）的能力而闻名。本研究旨在探讨依洛尤单抗单独或联合阿托伐他汀对动脉粥样硬化进展的影响。50 只雄性家兔随机分为 5 组：对照组、高胆固醇饮食组、依洛尤单抗溶媒组（二甲基亚砜，DMSO）、依洛尤单抗组和依洛尤单抗联合阿托伐他汀组。测量血清白细胞介素 10（IL-10）、IL-17、IL-1β、细胞间黏附分子（ICAM）和血管细胞黏附分子（VCAM）水平。使用流式细胞术评估单核细胞上的 Toll 样受体（TLR）表达。还进行了组织病理学检查和内膜厚度（IT）测量。结果显示，依洛尤单抗在 5 周时使血脂谱产生统计学显著（p<0.05）降低，10 周时达到峰值。此外，抑制剂在 10 周时将 TLR 降低至 10.83±1.8，将内膜厚度降低至 160.66±9.45。依洛尤单抗治疗显著降低了 IL-17、IL-1β、ICAM 和 VCAM，改善了主动脉壁的组织病理学变化。依洛尤单抗和阿托伐他汀联合使用导致 10 周时 TLR 更具统计学显著降低至 5.08±1.2，内膜厚度降低至 121.79±5.3。IL-17、IL-1β、ICAM 和 VCAM 显著（p<0.05）降低，主动脉壁的组织病理学变化显著改善。总之，依洛尤单抗通过调节炎症途径延缓动脉粥样硬化的进展。
