4.6 Article

The Association of Proprotein Convertase Subtilisin/Kexin Type 9 to Plasma Low-Density Lipoproteins: An Evaluation of Different Methods

期刊

METABOLITES
卷 11, 期 12, 页码 -

出版社

MDPI
DOI: 10.3390/metabo11120861

关键词

PCSK9; lipids; LDL; cardiovascular diseases; atherosclerosis; lipoproteins

资金

  1. Fondazione Cariplo [2015-0524, 2015-0564]
  2. H2020 REPROGRAM [PHC-03-2015/667837-2]
  3. ERANET [ER-2017-2364981]
  4. PRIN [2017H5F943]
  5. Ministry of Health-IRCCS MultiMedica [GR-2011-02346974]
  6. SISA Lombardia
  7. Fondazione SISA
  8. European Union's Horizon 2020 research and innovation program under the ERA-Net Cofund action [727565]
  9. Cibo, Microbiota, Salute by Vini di Batasiolo S.p.A [AL_RIC19ABARA_01]
  10. Post-Doctoral Fellowship 2020 by Fondazione Umberto Veronesi [2020-3318]
  11. Russian Ministry of Science and Higher Education [075-15-2020-901]

向作者/读者索取更多资源

This study aimed to investigate the interaction between PCSK9 and LDL, and found that PCSK9 interacts with a subfraction of LDL, with a binding percentage ranging from 2% to 30%, which is not correlated with plasma or LDL cholesterol levels. The association of PCSK9 with LDL appears to be sensitive to high salt concentrations. FPLC and iodixanol gradient ultracentrifugation are identified as the most suitable methods for studying this association.
Proprotein convertase subtilisin/kexin type-9 (PCSK9) is key regulator of low-density lipoprotein (LDL) metabolism. A significant proportion of PCSK9 is believed to be associated with LDL in plasma as it circulates, although this finding is still a matter of debate. The purpose of this study was to establish an experimental method to investigate the presence of such an interaction in the bloodstream. We compared a number of well-established methods for lipoprotein (LP) isolation to clarify whether PCSK9 associates differently to circulating lipoproteins, such as KBr gradient ultracentrifugation, physical precipitation of ApoB-LPs, fast protein liquid chromatography (FPLC) and iodixanol gradient ultracentrifugation. Our data show heterogeneity in PCSK9 association to lipoproteins according to the method used. Two methods, iodixanol ultracentrifugation and column chromatography, which did not involve precipitation or high salt concentration, consistently showed an interaction of PCSK9 with a subfraction of LDL that appeared to be more buoyant and have a lower size than average LDL. The percent of PCSK9 association ranged from 2 to 30% and did not appear to correlate to plasma or LDL cholesterol levels. The association of PCSK9 to LDL appeared to be sensitive to high salt concentrations. FPLC and iodixanol gradient ultracentrifugation appeared to be the most suitable methods for the study of this association.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据