Homma Koichiro, Homma Yasuhiko, Yoshida Tadashi, Ozawa Hideki, Shiina Yutaka, Wakino Shu, Hayashi Koichi, Itoh Hiroshi, Hori Shingo
Department of Internal Medicine, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan; Department of Emergency Medicine, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan.
Department of Clinical Health Science, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Japan.
J Clin Lipidol. 2015 Mar-Apr;9(2):210-6. doi: 10.1016/j.jacl.2014.12.007. Epub 2014 Dec 16.
Plasma levels of low-density lipoproteins (LDLs) are decreased through stimulation of their hepatic uptake by statins via an LDL receptor. However, it is unclear whether statins equally stimulate the hepatic uptake of all LDL subfractions.
We compared the effects of atorvastatin on 3 LDL subfractions, and their associations with LDL-receptor activities, in Japanese patients with polygenic hypercholesterolemia (PHC), familial combined hyperlipoproteinemia (FCHL), and familial hypercholesterolemia (FH).
Atorvastatin was administered to patients with PHC (n = 11), FCHL (n = 16), and FH (n = 13). We measured plasma levels of lipids, remnant-like particle cholesterol, apoproteins, and cholesterol in lipoprotein fractions. Sequential ultracentrifugation was performed to subfractionate the plasma lipoproteins, and lymphocyte LDL-receptor activities were estimated using flow cytometry.
The average daily dosage of atorvastatin was 10, 27, and 40 mg in patients with PHC, FCHL, and FH, respectively; after 12 months of atorvastatin treatment, LDL cholesterol (LDL-C) plasma levels decreased by 44%, 50%, and 53%, respectively (all, P < .0001). Atorvastatin reduced low-density LDL-C plasma levels in patients with PHC (48% reduction), FCHL (53%), and FH (46%) (all, P < .0001). Plasma levels of medium-density and high-density LDL-C were also significantly reduced in the 3 patient groups (all, P ≤ .0147). LDL-receptor activity was negatively correlated with baseline levels of medium-density LDL-C and with the decreases in plasma md-LDL-C levels.
Atorvastatin decreased the levels of the 3 LDL fractions. The md-LDL decrease appeared to be mainly because of stimulation of LDL-receptor activity.
他汀类药物通过低密度脂蛋白（LDL）受体刺激肝脏摄取LDL，从而降低血浆LDL水平。然而，尚不清楚他汀类药物是否能同等程度地刺激所有LDL亚组分的肝脏摄取。
我们比较了阿托伐他汀对日本多基因高胆固醇血症（PHC）、家族性混合性高脂血症（FCHL）和家族性高胆固醇血症（FH）患者的3种LDL亚组分的影响，以及它们与LDL受体活性的相关性。
对PHC患者（n = 11）、FCHL患者（n = l6）和FH患者（n = 13）给予阿托伐他汀治疗。我们测量了血浆脂质、残粒样颗粒胆固醇、载脂蛋白以及脂蛋白组分中的胆固醇水平。采用连续超速离心法对血浆脂蛋白进行亚组分分离，并使用流式细胞术评估淋巴细胞LDL受体活性。
PHC、FCHL和FH患者的阿托伐他汀平均日剂量分别为10、27和40mg；阿托伐他汀治疗12个月后，血浆LDL胆固醇（LDL-C）水平分别下降了44%、50%和53%（均P <.0001）。阿托伐他汀降低了PHC患者（降低48%）、FCHL患者（降低53%）和FH患者（降低46%）的低密度LDL-C血浆水平（均P <.0001）。3组患者的中密度和高密度LDL-C血浆水平也显著降低（均P≤.0147）。LDL受体活性与中密度LDL-C的基线水平以及血浆中密度LDL-C水平的降低呈负相关。
阿托伐他汀降低了3种LDL组分的水平。中密度LDL的降低似乎主要是由于LDL受体活性受到刺激。
