Mature proprotein convertase subtilisin/kexin type 9, coronary atheroma burden, and vessel remodeling in heterozygous familial hypercholesterolemia
Mature proprotein convertase subtilisin/kexin type 9, coronary atheroma burden, and vessel remodeling in heterozygous familial hypercholesterolemia
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DOI：
10.1016/j.jacl.2017.01.005
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发表时间：
2017-04-01
影响因子：
4.4
通讯作者：
Yasuda, Satoshi
中科院分区：
文献类型：
--
作者：
Kataoka, Yu;Harada-Shiba, Mariko;Yasuda, Satoshi
背景：蛋白转化酶枯草素/激酶9型（PCSK9）是杂合子家族性高胆固醇血症（HeFH）低密度脂蛋白代谢的重要贡献者，具有直接的促动脉粥样硬化作用。PCSK9以成熟形式和糠醛裂解形式存在，其生物活性不同。然而，是否每种PCSK9亚型具有不同的动脉粥样硬化特性仍有待阐明。目的：探讨不同PCSK9亚型与HeFH患者冠状动脉粥样硬化的关系。方法：对138例合并冠状动脉疾病的HeFH患者的204个非罪魁祸首节段进行血管内超声检查。采用酶联免疫吸附法（BML Inc., Tokyo, Japan）测定成熟的、furin裂解的PCSK9和PCSK9亚型的总浓度。研究了这些PCSK9值与血管内超声测量的关系。结果：成熟PCSK9水平与动脉粥样硬化体积百分比呈正相关（PANT: r = 0.78, P = 0.003）。尽管在较高的成熟PCSK9水平下存在广泛的动脉粥样硬化，但血管体积在任何成熟PCSK9水平下都没有改变（r = 0.05, P = 0.78）。这些反应导致更小的管腔容积，这与成熟PCSK9水平负相关（r = 0.65, P = 0.009）。相比之下，PAV与furin cleaved （r = 0.12, P = 0.45）和总PCSK9 （r = 0.37, P = 0.25）水平无显著相关。在多因素分析中，成熟PCSK9水平独立影响PAV（优势比：1.45,95%可信区间：1.11-1.67,P = 0.01）。即使是低密度脂蛋白胆固醇水平的受试者
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9), an important contributor to low-density lipoprotein metabolism in heterozygous familial hypercholesterolemia (HeFH), exhibits direct proatherogenic effects. PCSK9 circulates as mature and furin-cleaved forms, which differ in its biological activity. However, it remains to be elucidated whether each PCSK9 subtype has different atherogenic properties.OBJECTIVE: To investigate the association of each PCSK9 subtype with coronary atherosclerosis in HeFH.METHODS: About 204 nonculprit segments in 138 HeFH subjects with coronary artery disease were evaluated by using intravascular ultrasound. Mature, furin-cleaved PCSK9 and total concentration of PCSK9 subtypes were measured by using enzyme-linked immunosorbent assay (BML Inc., Tokyo, Japan). The relationship of these PCSK9 values with intravascular ultrasound measures was investigated.RESULTS: Mature PCSK9 level was positively associated with percent atheroma volume (PANT: r = 0.78, P =.003). Despite extensive atheroma under a higher mature PCSK9 level, vessel volume did not change across any mature PCSK9 levels (r = 0.05, P = .78). These responses resulted in smaller lumen volume, which was negatively correlated to mature PCSK9 level (r = 0.65, P = .009). By contrast, there were no significant relationships of PAV with furin-cleaved (r = 0.12, P = .45) and total PCSK9 (r = 0.37, P = .25) levels. On multivariate analysis, mature PCSK9 level independently contributed to PAV (odds ratio: 1.45, 95% confidence interval: 1.11-1.67, P = .01). Even in subjects with low-density lipoprotein cholesterol level