https://scholars.lib.ntu.edu.tw/handle/123456789/595754
標題: | Proprotein convertase substilisin/kexin type 9 antagonism reduces low-density lipoprotein cholesterol in statin-treated hypercholesterolemic nonhuman primates | 作者: | Liang, Hong Chaparro-Riggers, Javier Strop, Pavel Geng, Tao Sutton, Janette E DANIEL FU-CHANG TSAI Bai, Lanfang Abdiche, Yasmina Dilley, Jeanette Yu, Jessica Wu, Si Chin, S Michael Lee, Nicole A Rossi, Andrea Lin, John C Rajpal, Arvind Pons, Jaume Shelton, David L |
關鍵字: | SECRETED PCSK9; FAMILIAL HYPERCHOLESTEROLEMIA; LDL CHOLESTEROL; SUBTILISIN/KEXIN TYPE-9; PLASMA-CHOLESTEROL; IN-VIVO; RECEPTOR; MICE; GENE; DEGRADATION | 公開日期: | 二月-2012 | 出版社: | AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS | 卷: | 340 | 期: | 2 | 起(迄)頁: | 228 | 來源出版物: | Journal of Pharmacology and Experimental Therapeutics | 摘要: | Proprotein convertase substilisin/kexin type 9 (PCSK9) promotes the degradation of low-density lipoprotein (LDL) receptor (LDLR) and thereby increases serum LDL-cholesterol (LDL-C). We have developed a humanized monoclonal antibody that recognizes the LDLR binding domain of PCSK9. This antibody, J16, and its precursor mouse antibody, J10, potently inhibit PCSK9 binding to the LDLR extracellular domain and PCSK9-mediated down-regulation of LDLR in vitro. In vivo, J10 effectively reduces serum cholesterol in C57BL/6 mice fed normal chow. J16 reduces LDL-C in healthy and diet-induced hypercholesterolemic cynomologous monkeys, but does not significantly affect high-density lipoprotein-cholesterol. Furthermore, J16 greatly lowered LDL-C in hypercholesterolemic monkeys treated with the HMG-CoA reductase inhibitor simvastatin. Our data demonstrate that anti-PCSK9 antibody is a promising LDL-C-lowering agent that is both efficacious and potentially additive to current therapies. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/595754 | ISSN: | 0022-3565 1521-0103 |
DOI: | 10.1124/jpet.111.187419 |
顯示於: | 醫學教育暨生醫倫理學科所 |
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