The New Molecular Entity Evolocumab, One Kind of PCSK9 Inhibitor, Reduce Plasma Small Size LDL-Cholesterol Levels by Using a New Standardized Method of Measuring LDL Size
The New Molecular Entity Evolocumab, One Kind of PCSK9 Inhibitor, Reduce Plasma Small Size LDL-Cholesterol Levels by Using a New Standardized Method of Measuring LDL Size
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新分子实体 Evolocumab 是一种 PCSK9 抑制剂，通过使用测量 LDL 大小的新标准化方法来降低血浆小大小 LDL 胆固醇水平
DOI：
10.4236/ojmip.2017.71001
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发表时间：
2017
影响因子：
2.1
通讯作者：
Mistuhiko Noda
中科院分区：
文献类型：
--
作者：
I. Inoue;R. Kubota;Shohan Yanagi;M. Akita;Takanari Nakano;S. Katayamá;A. Shimada;Mistuhiko Noda
目的：目前尚无证据表明蛋白转换酶枯草杆菌/可信9型(PCSK9)抑制剂evocumab对小体积低密度脂蛋白的影响。我们使用脂蛋白分析的PAGE系统观察了挥发单抗对低密度脂蛋白亚组分颗粒直径的疗效和副作用。方法：我们定义了30例高危高脂血症患者。用3%非变性聚丙烯酰胺凝胶电泳法(3%PAGE)、2%~16%非变性聚丙烯酰胺梯度凝胶电泳法(2%~16%GGE)和2.7%~5%GGE法分析低密度脂蛋白亚组分。葛根单抗140 mg/d联合他汀类药物治疗4周后，血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)均显著改善。结果：总胆固醇、甘油三酯、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇水平分别提高了33%、20%、10%和54%。低密度脂蛋白的平均直径从25.6±0.4 nm增加到26.4±0.8 nm。小而致密的低密度脂蛋白-胆固醇(sdLDL-C)、大上升的低密度脂蛋白-胆固醇(lbLDL-C)和中段脂蛋白-胆固醇分别降低。因此，对这篇论文的初步研究可以作为对脂代谢世界的新洞察的第一步。结论：在他汀类药物治疗的基础上短期给药，可显著降低小体积低密度脂蛋白水平。
Aims: There has been no evidence on the effects of evolocumab, protein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, on small size LDL. We observationally investigated the efficacy and side effects of evolocumab on the LDL subfraction particle diameter using PAGE system for lipoprotein analysis. Methods: We defined 30 patients with high-risk hyperlipidemia. As for analysis of LDL subfraction profile, we used polyacrylamide gel electrophoresis three methods: 1) 3% nondenatured poly-acrylamide gel electrophoresis method (3%PAGE), 2) 2% - 16% nondenatured poly-acrylamide gradient gel electro-phoresis method (2% - 16% GGE) and 3) 2.7% - 5% GGE. Evolocumab 140 mg/day administered together with statin significantly improved serum total cholesterol (TC), triglyceride (TG), high-dense lipoprotein-cholesterol (HDL-C), and LDL-C after four-week treatment. Results: TC, TG, HDL-C and LDL-C levels were improved by, respectively, 33%, 20%, 10%, and 54%. The mean LDL size significantly increased from 25.6 ± 0.4 nm to 26.4 ± 0.8 nm. The small dense LDL-cholesterol (sdLDL-C), large buoyant LDL-cholesterol (lbLDL-C), and mid-band lipoprotein-cholesterol were reduced, respectively. Therefore, the preliminary study on this paper can be the first step into a new insight on the world of lipid metabolism. Conclusion: Short-term administration of evolocumab addedons to statin therapy, significantly reduced small size LDL levels.
DOI：
10.1001/jama.1988.03410130125037
发表时间：
1988-10
期刊：
JAMA
影响因子：
--
作者：
M. Austin;J. Breslow;C. Hennekens;Julie E. Buring;W. Willett;R. Krauss
通讯作者：
M. Austin;J. Breslow;C. Hennekens;Julie E. Buring;W. Willett;R. Krauss
关于PCSK9的功能和稳态：与LDLR的相互相互作用和其他脂质效应。
影响因子：
5.3
作者：
Tavori H;Rashid S;Fazio S
通讯作者：
Fazio S