Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, via Balzaretti 9, 20133, Milan, Italy; S.I.S.A. Center for the Study of Atherosclerosis - Bassini Hospital, Cinisello Balsamo, Milan, Italy.
IRCCS MultiMedica, via Fantoli 16, 20138, Milan, Italy.
Pharmacol Res. 2018 Apr;130:1-11. doi: 10.1016/j.phrs.2018.01.025. Epub 2018 Feb 8.
After more than a decade of intense investigation, Pro-protein Convertase Subtilisin-Kexin type 9 (PCSK9) remains a hot topic of research both at experimental and clinical level. Interestingly PCSK9 is expressed in different tissues suggesting the existence of additional function(s) beyond the modulation of the Low-Density Lipoprotein (LDL) receptor in the liver. Emerging data suggest that PCSK9 might play a role in the modulation of triglyceride-rich lipoprotein (TGRL) metabolism, mainly Very Low-Density Lipoproteins (VLDL) and their remnants. In vitro, PCSK9 affects TGRLs production by intestinal cells as well as the catabolism of LDL receptor homologous and non-homologous targets such as VLDL receptor, CD36 and ApoE2R. However, the in vivo relevance of these findings is still debated. This review aims at critically discussing the role of PCSK9 on TGRLs metabolism with a major focus on the impact of its genetic and pharmacological modulation on circulating lipids and lipoproteins beyond LDL.
经过十多年的深入研究，前蛋白转化酶枯草溶菌素 9（PCSK9）仍然是实验和临床研究的热门课题。有趣的是，PCSK9 在不同的组织中表达，这表明其在肝脏中调节低密度脂蛋白（LDL）受体之外存在其他功能。新出现的数据表明，PCSK9 可能在富含甘油三酯的脂蛋白（TGRL）代谢的调节中发挥作用，主要是极低密度脂蛋白（VLDL）及其残基。在体外，PCSK9 影响肠道细胞中 TGRL 的产生，以及 LDL 受体同源和非同源靶标如 VLDL 受体、CD36 和 ApoE2R 的代谢。然而，这些发现的体内相关性仍存在争议。本综述旨在批判性地讨论 PCSK9 在 TGRLs 代谢中的作用，重点讨论其遗传和药理学调节对循环脂质和脂蛋白（LDL 以外）的影响。
