Okada Takeshi, Ohama Tohru, Okazaki Mitsuyo, Kanno Kotaro, Matsuda Hibiki, Sairyo Masami, Zhu Yinghong, Saga Ayami, Kobayashi Takuya, Masuda Daisaku, Koseki Masahiro, Nishida Makoto, Sakata Yasushi, Yamashita Shizuya
Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
Department of Dental Anesthesiology, Osaka University Graduate School of Dentistry, Osaka, Japan.
PLoS One. 2018 Jan 5;13(1):e0190875. doi: 10.1371/journal.pone.0190875. eCollection 2018.
We previously reported that patients with cholesteryl ester transfer protein (CETP) deficiency (CETP-D) have a higher prevalence of atherosclerotic cardiovascular disease, in spite of increased HDL-C levels. However, characterization of HDL in CETP-D has not been well described. Therefore, we examined HDL particle number (PN) rather than HDL-C level.
Nine patients with CETP-D and 9 normolipidemic subjects were enrolled. We performed gel permeation high-performance liquid chromatography (GP-HPLC) analysis, determined the cholesterol and triglyceride composition of all lipoprotein subclasses, and calculated the PN of each subclass, which consisted of 3 VLDL (large, medium, and small), 4 LDL (large, medium, small, and very small), and 5 HDL (very large, large, medium, small, and very small) subclasses. The PNs of large and medium LDL were significantly lower in CETP-D than that in healthy subjects (0.66- and 0.63-fold decrease, respectively; p<0.001), whereas the PN of very small LDL, which is known to be atherogenic, was significantly higher (1.36-fold increase, p = 0.016). The PNs of very large and large HDL in CETP-D were markedly higher than that in healthy subjects (19.9- and 4.5-fold increase, respectively; p<0.001), whereas the PNs of small and very small HDL, which have more potent anti-atherogenic functions, were significantly lower (0.76- and 0.61-fold decrease, respectively; p<0.001).
We have assessed the PNs of detailed subclasses of patients with CETP-D for the first time. The PN of larger HDL was markedly increased, that of smaller HDL was decreased, and that of very small LDL was increased, suggesting that CETP-D has pro-atherogenic lipoprotein properties.
我们之前报道过，尽管胆固醇酯转运蛋白（CETP）缺乏症（CETP-D）患者的高密度脂蛋白胆固醇（HDL-C）水平升高，但其动脉粥样硬化性心血管疾病的患病率更高。然而，CETP-D中HDL的特征尚未得到充分描述。因此，我们检测了HDL颗粒数量（PN）而非HDL-C水平。
纳入9例CETP-D患者和9名血脂正常的受试者。我们进行了凝胶渗透高效液相色谱（GP-HPLC）分析，测定了所有脂蛋白亚类的胆固醇和甘油三酯组成，并计算了每个亚类的PN，每个亚类包括3种极低密度脂蛋白（VLDL，大、中、小）、4种低密度脂蛋白（LDL，大、中、小、极小）和5种高密度脂蛋白（HDL，极大、大、中、小、极小）亚类。CETP-D患者中大、中型LDL的PN显著低于健康受试者（分别降低0.66倍和0.63倍；p<0.001），而已知具有致动脉粥样硬化作用的极小LDL的PN显著更高（增加1.36倍，p = 0.016）。CETP-D患者中极大和大型HDL的PN显著高于健康受试者（分别增加19.9倍和4.5倍；p<0.001），而具有更强抗动脉粥样硬化功能的小型和极小HDL的PN显著更低（分别降低0.76倍和0.61倍；p<0.001）。
我们首次评估了CETP-D患者详细亚类的PN。较大HDL的PN显著增加，较小HDL的PN降低，极小LDL的PN增加，提示CETP-D具有促动脉粥样硬化的脂蛋白特性。
