Evolocumab是一种抑制protein convertase subtilisin/kexin type 9（PCSK9）的人源单克隆抗体。
Cas No.:1256937-27-5
Sample solution is provided at 25 µL, 10mM.
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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]。
| Cell experiment [1]: | |
Cell lines | Human umbilical vein endothelial cells (HUVEC) |
Preparation Method | For assessment of HUVECs viability, MTT [3-(4,5-dimethylthia-zol-2-yl)-2,5-diphenyltetrazolium bromide] kit was used. Briefly, the cells were seeded at 1×105 cells per well in the 96-well plates and pre-treated, with Evolocumab at the concentration range of 0.5–100mg/ml in the logarithmic growth phase. After 24h incubation, for preventing any direct interaction between the test drug and H2O2, the medium of each well was removed and the cells were washed out with phosphate buffered saline (PBS). After that, new medium was added to the wells and HUVEC were exposed to 0.5mM H2O2 for 2h. Then MTT reagent was added and the cells were cultivated for 4h followed by dissolving the fora-mazan crystals resulting from MTT reaction with living cells with dimethyl sulfoxide. Finally, the absorbance was detected by a microplate reader at 570nm. |
Reaction Conditions | 0.5–100mg/ml; 24h |
Applications | Evolocumab pretreatment significantly reduced the cytotoxicity of human umbilical vein endothelial cells (HUVEC) induced by hydrogen peroxide (H2O2). |
| Animal experiment [2]: | |
Animal models | Wild-type (WT) C57BL/6J mice (Myocardial ischemia‒reperfusion (I/R) model) |
Preparation Method | I/R surgery: WT mice were placed in the supine position after anesthetized with ketamine (0.2g/kg) and xylazine (0.01g/kg) via intraperitoneal injection. To expose heart, the skin of left chest was disinfected and incised through the third or fourth intercostal space after blunt dissection of the chest wall. The left anterior descending coronary artery (LAD) was obturated with a slipknot made with a nylon silk suture, positioned 2mm above the inferior margin of the left auricle. Myocardial ischemia was indicated by observing the color of the myocardium below the knot site, which changed from red to pale. After 30min of ligation, the slipknot was loosened to allow reperfusion for 72h. Mice received subcutaneously injections of Evolocumab (PCSK9 inhibitor, 10mg/kg), the first and second times were 7 days and 30min before surgery, respectively, and an equivalent volume of saline was used for the control group. The recombinant adeno-associated virus 9 (rAAV9) with siRNA was selected to perform myocardial-specific knockdown of LIAS, and the rAAV9-siLIAS or rAAV9-sicontrol was administrated to mice by tail intravenous injection at 3 weeks before I/R surgery. After 72h of reperfusion, the cardiac function was estimated by echocardiography with Vevo 1100 system. |
Dosage form | 10mg/kg/day; twice; subcutaneously injections |
Applications | Evolocumab treatment significantly improved the cardiac injury and functional impairment in mice with coronary artery disease (I/R). |
References: | |
| Cas No. | 1256937-27-5 | SDF | Download SDF |
| 别名 | 依洛尤单抗,AMG 145; Repatha | ||
| 分子式 | 分子量 | ||
| 溶解度 | 储存条件 | Store at 4°C, protect from light | |
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