Ohmura Hirotoshi, Mokuno Hiroshi, Sawano Masato, Hatsumi Chie, Mitsugi Yasushi, Watanabe Yoshiro, Daida Hiroyuki, Yamaguchi Hiroshi
Department of Cardiology, Juntendo University School of Medicine, Tokyo, Japan.
Metabolism. 2002 Sep;51(9):1081-7. doi: 10.1053/meta.2002.34695.
An increased susceptibility of low-density lipoprotein (LDL) to lipid peroxidative modification may be a key factor in the higher risk of coronary artery disease (CAD) among subjects with phenotype B. Compositional differences in the LDL particle may also be implicated in its atherogenicity and, in particular, may be associated with varying degrees of oxidative susceptibility of LDL, although this remains unclear. We hypothesized that the oxidative susceptibility of small, dense LDL was directly influenced by its lipid composition, which may lead to an increased risk of CAD in subjects with phenotype B. To test this hypothesis, we compared the differences in lipid compositions of LDL particles from subjects with phenotype A and those with phenotype B, and investigated the direct association of lipid composition with susceptibility to lipid peroxidative modification in 102 subjects who underwent a coronary angiographic examination. Subjects with phenotype B (n = 52) had a significantly higher incidence of CAD than subjects with phenotype A (77% v 44%; P <.005). In comparing the oxidative susceptibility of LDL, the lag time was significantly reduced in subjects with phenotype B compared to phenotype A (48.7 +/- 8.6 v 41.5 +/- 5.5 minutes; P <.0001). In addition, the lag time showed a positive correlation with LDL-peak particle diameter (PPD) (r = 0.324, P <.005). Lipid composition per LDL particle was expressed as the ratio of lipid content to apolipoprotein B (apoB) content (wt/wt). Subjects with phenotype B showed a significant depletion in the contents of free-cholesterol (FC), cholesterol ester (CE), and phospholipid (PL) per particle compared to subjects with phenotype A, although there was no significant difference in the triglyceride (TG) content per LDL particle. Except for TG, the lipid content per LDL particle showed a significant positive correlation with lag time in all subjects. Moreover, increased susceptibility of small, dense LDL to lipid peroxidative modification was most strongly associated with a depleted FC content per LDL particle. In conclusion, the greater risk of CAD in subjects with phenotype B may result, in part, from increased susceptibility to lipid peroxidative modification of LDL that is depleted in lipid contents, especially FC content per LDL particle.
低密度脂蛋白（LDL）对脂质过氧化修饰的易感性增加可能是B型表型受试者冠心病（CAD）风险较高的关键因素。LDL颗粒的成分差异也可能涉及其致动脉粥样硬化性，特别是可能与LDL不同程度的氧化易感性有关，尽管这一点仍不清楚。我们假设小而密LDL的氧化易感性直接受其脂质成分影响，这可能导致B型表型受试者CAD风险增加。为验证这一假设，我们比较了A型表型和B型表型受试者LDL颗粒的脂质成分差异，并在102例接受冠状动脉造影检查的受试者中研究了脂质成分与脂质过氧化修饰易感性的直接关联。B型表型受试者（n = 52）的CAD发病率显著高于A型表型受试者（77%对44%；P <.005）。在比较LDL的氧化易感性时，与A型表型相比，B型表型受试者的延迟时间显著缩短（48.7±8.6对41.5±5.5分钟；P <.0001）。此外，延迟时间与LDL峰值颗粒直径（PPD）呈正相关（r = 0.324，P <.005）。每个LDL颗粒的脂质成分表示为脂质含量与载脂蛋白B（apoB）含量的比值（重量/重量）。与A型表型受试者相比，B型表型受试者每个颗粒的游离胆固醇（FC）、胆固醇酯（CE）和磷脂（PL）含量显著减少，尽管每个LDL颗粒的甘油三酯（TG）含量无显著差异。除TG外，所有受试者中每个LDL颗粒的脂质含量与延迟时间呈显著正相关。此外，小而密LDL对脂质过氧化修饰的易感性增加与每个LDL颗粒中FC含量减少密切相关。总之，B型表型受试者CAD风险较高可能部分归因于脂质含量尤其是每个LDL颗粒中FC含量减少的LDL对脂质过氧化修饰的易感性增加。
