Further LDL Cholesterol Lowering Through Targeting PCSK9 for Coronary Artery Disease
Further LDL Cholesterol Lowering Through Targeting PCSK9 for Coronary Artery Disease
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DOI：
10.2174/187153008786848286
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发表时间：
2008-12-01
影响因子：
1.9
通讯作者：
Konrad, Robert J.
中科院分区：
文献类型：
--
作者：
Cao, Guoqing;Qian, Yue-Wei;Konrad, Robert J.
前蛋白转化酶枯草杆菌蛋白酶/kexin 9型（PCSK 9）是一种丝氨酸蛋白酶，属于前蛋白转化酶家族。PCSK 9作为酶原合成，其前结构域通过其自身的催化活性裂解。切割的前结构域与内质网内的PCSK 9羧基末端的其余部分形成蛋白质复合物并被分泌。已显示分泌的PCSK 9能够在体外和体内降低低密度脂蛋白受体（LDLR）水平。因此，PCSK 9已成为调节LDLR水平和血浆LDL胆固醇的重要参与者。此外，PCSK 9缺乏导致人体LDL胆固醇水平显著降低，并对冠心病提供显著保护。本文就PCSK 9作为降低LDL胆固醇预防和治疗冠心病的治疗靶点的研究进展作一综述。
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that belongs to the proprotein convertase family. PCSK9 is synthesized as a zymogen and its prodomain is cleaved by its own catalytic activity. The cleaved prodomain forms a protein complex with the rest of the PCSK9 carboxyl terminus within the endoplasmic reticulum and is secreted. Secreted PCSK9 has been shown to be able to reduce low-density lipoprotein receptor ( LDLR) levels in vitro and in vivo. Thus PCSK9 has emerged as an important player modulating LDLR levels and plasma LDL cholesterol. Furthermore, PCSK9 deficiency leads to significantly lowered LDL cholesterol levels in humans and provides dramatic protection against coronary heart disease. We review here the current understanding of PCSK9 and its potential as a therapeutic target through which to reduce LDL cholesterol for prevention and treatment of coronary heart disease.