Serum proprotein convertase subtilisin Kexin type 9 is correlated directly with serum LDL cholesterol
Serum proprotein convertase subtilisin Kexin type 9 is correlated directly with serum LDL cholesterol
复制标题
DOI：
10.1373/clinchem.2007.091280
复制
发表时间：
2007-10-01
影响因子：
9.3
通讯作者：
Konrad, Robert J.
中科院分区：
文献类型：
--
作者：
Alborn, William E.;Cao, Guoqing;Konrad, Robert J.
背景：前蛋白转化酶枯草杆菌蛋白酶kexin 9型（PCSK 9）作为血清LDL-胆固醇（LDLC）的关键调节剂正受到关注。这种新的丝氨酸蛋白酶通过未知的机制引起肝LDL受体的降解。在人类中，PCSK 9基因中的功能获得性突变导致一种形式的家族性高胆固醇血症，而功能丧失性突变导致LDLC显著降低和心血管风险降低。方法：用重组人PCSK 9蛋白和2株抗PCSK 9单克隆抗体建立双抗体夹心ELISA法。我们测量了55份人血清样本中的PCSK 9和脂质，并将结果进行了关联。我们使用抗PCSK 9抗体来测定通过连续浮选超离心分离的脂蛋白颗粒级分。PCSK 9的血清浓度范围为11 - 115 μ g/L，与LDLC的血清浓度直接相关（r = 0.45，P = 0.001）和总胆固醇（Q = 0.50，P = 0.0003），但不与甘油三酯（r 0.15，P = 0.28）或HDL胆固醇浓度（r 0.13，P = 0.36）。在任何脂蛋白中均未检出PCSK 9。结论：PCSK 9存在于人血清中，可能与特定的脂蛋白颗粒无关。人PCSK 9的循环浓度与LDL和总胆固醇浓度直接相关。(C)2007年美国临床化学协会
Background: Proprotein convertase subtilisin kexin type 9 (PCSK9) is gaining attention as a key regulator of serum LDL-cholesterol (LDLC). This novel serine protease causes the degradation of hepatic LDL receptors by an unknown mechanism. In humans, gain-of-function mutations in the PCSK9 gene cause a form of familial hypercholesterolemia, whereas loss-of-function mutations result in significantly decreased LDLC and decreased cardiovascular risk. Relatively little is known about PCSK9 in human serum.Methods: We used recombinant human PCSK9 protein and 2 different anti-PCSK9 monoclonal antibodies to build a sandwich ELISA. We measured PCSK9 and lipids in 55 human serum samples and correlated the results. We used the anti-PCSK9 antibodies to assay lipoprotein particle fractions separated by sequential flotation ultracentrifugation.Results: Serum concentrations of PCSK9 ranged from 11 to 115 mu g/L and were directly correlated with serum concentrations of LDLC (r = 0.45, P = 0.001) and total cholesterol Q = 0.50, P = 0.0003), but not with triglycerides (r 0.15, P = 0.28) or HDL cholesterol concentrations (r 0.13, P = 0.36). PCSK9 was not detectable in any lipoprotein. particle fraction, including LDL.Conclusions: PCSK9 is present in human serum, likely not associated with specific lipoprotein particles. The circulating concentrations of human PCSK9 are diiectly correlated with LDL and total cholesterol concentrations. (C) 2007 American Association for Clinical Chemistry