Evolocumab is a human monoclonal antibody that inhibits protein convertase subtilisin/kexin type 9 (PCSK9) [1]. PCSK9 is a secreted protein that can bind to low-density lipoprotein receptor (LDLR) and transport it to the lysosomal degradation pathway. Evolocumab binds to the circulating PCSK9 protein, which can inhibit its binding to LDLR [2-3]. Evolocumab can be used in the research of hypercholesterolemia and atherosclerotic cardiovascular diseases [4].
In vitro, Evolocumab (0.5–100mg/ml; 24h) pretreatment significantly reduced the cytotoxicity of human umbilical vein endothelial cells (HUVEC) induced by hydrogen peroxide (H2O2), as well as the levels of hydrogen peroxide and MDA, and improved the iron-reducing antioxidant capacity (FRAP) in both intracellular and extracellular culture media [5]. Two hours before hypoxia/reoxygenation (H/R), pretreatment with Evolocumab (100μg/ml) inhibited the decline in AC16 cell viability induced by H/R and successfully reversed the upregulation of LIAS mRNA levels after H/R [6].
In vivo, Evolocumab (10mg/kg/day; twice; s.c.) treatment significantly improved the cardiac injury and functional impairment, inflammation, and oxidative stress in mice with coronary artery disease (I/R) injury, blocked PCSK9, and inhibited the increase in the ratio of infarct area/risk area of I/R [6]. A single-dose treatment with Evolocumab (1, 5, 10mg/kg/day; i.v.) significantly alleviated cerebral infarction and neurological dysfunction in mice with middle cerebral artery occlusion/reperfusion (MCAO/R) model, upregulated the expression of occludin and claudin-5, and significantly reduced the levels of platelet cells, ICAM-1, VCAM-1, and CD45 [7].
References:
[1] Fala L. Repatha (Evolocumab): Second PCSK9 Inhibitor Approved by the FDA for Patients with Familial Hypercholesterolemia. Am Health Drug Benefits. 2016 Mar;9(Spec Feature):136-9.
[2] Horton JD, Cohen JC, Hobbs HH. PCSK9: a convertase that coordinates LDL catabolism. J Lipid Res. 2009;50 Suppl(Suppl):S172-S177.
[3] Essalmani R, Weider E, Marcinkiewicz J, et al. A single domain antibody against the Cys-and His-rich domain of PCSK9 and evolocumab exhibit different inhibition mechanisms in humanized PCSK9 mice[J]. Biological chemistry, 2018, 399(12): 1363-1374.
[4] Li Z, Zhu H, Liu H, et al. Evolocumab loaded Bio-Liposomes for efficient atherosclerosis therapy[J]. Journal of Nanobiotechnology, 2023, 21(1): 158.
[5] Safaeian L, Mirian M, Bahrizadeh S. Evolocumab, a PCSK9 inhibitor, protects human endothelial cells against H2O2-induced oxidative stress[J]. Archives of physiology and biochemistry, 2022, 128(6): 1681-1686.
[6] Li ZZ, Guo L, An YL, et al. Evolocumab attenuates myocardial ischemia/reperfusion injury by blocking PCSK9/LIAS-mediated cuproptosis of cardiomyocytes. Basic Res Cardiol. 2025;120(2):301-320.
[7] Luo Y, Yuan L, Liu Z, et al. Inhibition of PCSK9 Protects against Cerebral Ischemia‒Reperfusion Injury via Attenuating Microcirculatory Dysfunction. Neurochem Res. 2024;50(1):10.
Evolocumab是一种抑制protein convertase subtilisin/kexin type 9（PCSK9）的人源单克隆抗体 [1]。PCSK9是一种分泌蛋白，它能够与低密度脂蛋白受体（LDLR）结合，并将其运送至溶酶体降解途径中。Evolocumab与循环的PCSK9蛋白结合，能够抑制其与LDLR结合 [2-3]。Evolocumab可用于高胆固醇血症和动脉粥样硬化性心血管疾病的研究 [4]。
在体外，Evolocumab（0.5–100mg/ml; 24h）预处理显著减少了过氧化氢（H2O2）诱导的人脐静脉内皮细胞（HUVEC）的细胞毒性和氢过氧化物和MDA水平，且提高了细胞内和细胞外培养基中的铁还原抗氧化能力（FRAP） [5]。在缺氧/再氧化（H/R）前2小时用Evolocumab（100μg/ml）预处理抑制了H/R诱导的AC16细胞活力下降并成功逆转了H/R后LIAS的mRNA 水平的上调 [6]。
在体内，Evolocumab（10mg/kg/day; twice; s.c.）治疗显著改善了冠状动脉疾病(I/R)损伤小鼠的心脏损伤和功能障碍、炎症和氧化应激，阻断了PCSK9并抑制了I/R的梗塞面积/风险面积比的增加 [6]。Evolocumab（1, 5, 10mg/kg/day; i.v.）单剂量治疗显著缓解了大脑中动脉闭塞/再灌注（MCAO/R)小鼠模型的脑梗死和神经功能障碍，上调了occludin和claudin-5的表达，并显著降低了血小板细胞、ICAM-1、VCAM-1和CD45水平 [7]。