PCSK9 Modulates the Secretion But Not the Cellular Uptake of Lipoprotein(a) Ex Vivo: An Effect Blunted by Alirocumab.
PCSK9 Modulates the Secretion But Not the Cellular Uptake of Lipoprotein(a) Ex Vivo: An Effect Blunted by Alirocumab.
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DOI：
10.1016/j.jacbts.2016.06.006
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发表时间：
2016-10-01
期刊：
影响因子：
--
通讯作者：
Lambert, Gilles
中科院分区：
文献类型：
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作者：
Villard, Elise F;Thedrez, Aurelie;Lambert, Gilles
为了阐明前蛋白转化酶枯草杆菌蛋白酶kexin 9型（PCSK9）抑制剂alirocumab如何调节脂蛋白（a）[Lp（a）]血浆水平，作者在原代人肝细胞和真皮成纤维细胞中进行了一系列Lp（a）摄取研究，并测量了人肝细胞的Lp（a）分泌。他们发现Lp（a）细胞摄取以低密度脂蛋白受体非依赖性方式发生。PCSK 9和alirocumab均未改变Lp（a）内化。相比之下，PCSK 9使人肝细胞的载脂蛋白（a）分泌急剧增加，alirocumab逆转了该效应。他们认为PCSK9并不显著调节Lp（a）催化剂，而是增强了Lp（a）从肝细胞的分泌。
To elucidate how the proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor alirocumab modulates lipoprotein(a) [Lp(a)] plasma levels, the authors performed a series of Lp(a) uptake studies in primary human hepatocytes and dermal fibroblasts and measured Lp(a) secretion from human hepatocytes. They found that Lp(a) cellular uptake occurred in a low-density lipoprotein receptor-independent manner. Neither PCSK9 nor alirocumab altered Lp(a) internalization. By contrast, the secretion of apolipoprotein (a) from human hepatocytes was sharply increased by PCSK9, an effect that was reversed by alirocumab. They propose that PCSK9 does not significantly modulate Lp(a) catabolism, but rather enhances the secretion of Lp(a) from liver cells.