On the function and homeostasis of PCSK9: reciprocal interaction with LDLR and additional lipid effects.
On the function and homeostasis of PCSK9: reciprocal interaction with LDLR and additional lipid effects.
复制标题
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。
DOI：
10.1016/j.atherosclerosis.2014.12.017
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发表时间：
2015-02
期刊：
影响因子：
5.3
通讯作者：
Fazio S
中科院分区：
文献类型：
--
作者：
Tavori H;Rashid S;Fazio S
前蛋白转化酶枯草杆菌蛋白酶kexin 9型（PCSK 9）是一种循环配体，可终止低密度脂蛋白（LDL）受体（LDLR）的生命周期，从而影响血浆LDL-胆固醇（LDL-C）水平。最近的证据表明，除了直接的作用机制外，PCSK 9、LDLR和血浆脂蛋白水平之间存在更复杂的相互作用，包括：（a）存在表面LDLR和血浆PCSK 9的平行和相互调节;（B）PCSK 9和LDL-C水平之间的相关性不仅取决于PCSK 9去除肝脏LDLR的事实，而且还由于高达40%的血浆PCSK 9与LDL物理结合的事实;和（c）血浆PCSK 9产生与富含脂蛋白酰亚胺的脂蛋白的组装和分泌之间的关联。PCSK 9对LDLR的作用正被成功用于开发降低血浆LDL-C水平的抗PCSK 9治疗。目前的生物化学研究已经发现了PCSK 9的其他作用机制和相互作用伙伴，这为更深入地了解这种有趣蛋白质的调节，代谢和作用开辟了道路。
Proprotein convertase subtilisin kexin type 9 (PCSK9) is a circulatory ligand that terminates the lifecycle of the low-density lipoprotein (LDL) receptor (LDLR) thus affecting plasma LDL-cholesterol (LDL-C) levels. Recent evidence shows that in addition to the straightforward mechanism of action, there are more complex interactions between PCSK9, LDLR and plasma lipoprotein levels, including: (a) the presence of both parallel and reciprocal regulation of surface LDLR and plasma PCSK9; (b) a correlation between PCSK9 and LDL-C levels dependent not only on the fact that PCSK9 removes hepatic LDLR, but also due to the fact that up to 40% of plasma PCSK9 is physically associated with LDL; and (c) an association between plasma PCSK9 production and the assembly and secretion of triglyceride-rich lipoproteins. The effect of PCSK9 on LDLR is being succesfuly utilized toward the development of anti-PCSK9 therapies to reduce plasma LDL-C levels. Current biochemical research has uncovered additional mechanisms of action and interacting partners for PCSK9, and this opens the way for a more thourough understanding of the regulation, metabolism, and effects of this interesting protein.