Tavori Hagai, Rashid Shirya, Fazio Sergio
The Knight Cardiovascular Institute, Center of Preventive Cardiology, Oregon Health and Sciences University, Portland, OR, USA.
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, and Saint John, New Brunswick, Canada.
Atherosclerosis. 2015 Feb;238(2):264-70. doi: 10.1016/j.atherosclerosis.2014.12.017. Epub 2014 Dec 17.
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 successfully 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 thorough understanding of the regulation, metabolism, and effects of this interesting protein.
前蛋白转化酶枯草溶菌素9型（PCSK9）是一种循环配体，它终止低密度脂蛋白（LDL）受体（LDLR）的生命周期，从而影响血浆低密度脂蛋白胆固醇（LDL-C）水平。最近的证据表明，除了直接的作用机制外，PCSK9、LDLR和血浆脂蛋白水平之间还存在更复杂的相互作用，包括：（a）表面LDLR和血浆PCSK9存在平行和相互调节；（b）PCSK9与LDL-C水平之间的相关性不仅取决于PCSK9清除肝脏LDLR这一事实，还因为高达40%的血浆PCSK9与LDL存在物理关联；（c）血浆PCSK9的产生与富含甘油三酯的脂蛋白的组装和分泌之间存在关联。PCSK9对LDLR的作用正成功地用于开发抗PCSK9疗法以降低血浆LDL-C水平。目前的生化研究揭示了PCSK9的其他作用机制和相互作用伙伴，这为更全面地理解这种有趣蛋白质的调节、代谢和作用开辟了道路。
