Guérin M, Le Goff W, Lassel T S, Van Tol A, Steiner G, Chapman M J
Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 321, Lipoproteines et Atherogenese, Hôpital de la Pitié, Paris, France.
Arterioscler Thromb Vasc Biol. 2001 Feb;21(2):282-8. doi: 10.1161/01.atv.21.2.282.
Plasma cholesteryl ester transfer protein (CETP) facilitates intravascular lipoprotein remodeling by promoting the heteroexchange of neutral lipids. To determine whether the degree of triglyceridemia may influence the CETP-mediated redistribution of HDL CE between atherogenic plasma lipoprotein particles in type 2 diabetes, we evaluated CE mass transfer from HDL to apoB-containing lipoprotein acceptors in the plasma of type 2 diabetes subjects (n=38). In parallel, we investigated the potential relationship between CE transfer and the appearance of an atherogenic dense LDL profile. The diabetic population was divided into 3 subgroups according to fasting plasma triglyceride (TG) levels: group 1 (G1), TG<100 mg/dL; group 2 (G2), 100<TG<200 mg/dL; and group 3 (G3), TG>200 mg/dL. Type 2 diabetes patients displayed an asymmetrical LDL profile in which the dense LDL subfractions predominated. Plasma levels of dense LDL subfractions were strongly positively correlated with those of plasma triglyceride (TG) (r=0.471; P:=0.0003). The rate of CE mass transfer from HDL to apoB-containing lipoproteins was significantly enhanced in G3 compared with G2 or G1 (46.2+/-8.1, 33.6+/-5.3, and 28.2+/-2.7 microg CE transferred. h(-1). mL(-1) in G3, G2, and G1, respectively; P:<0.0001 G3 versus G1, P:=0.0001 G2 versus G1, and P:=0.02 G2 versus G3). The relative capacities of VLDL and LDL to act as acceptors of CE from HDL were distinct between type 2 diabetes subgroups. LDL particles represented the preferential CE acceptor in G1 and accounted for 74% of total CE transferred from HDL. By contrast, in G2 and G3, TG-rich lipoprotein subfractions accounted for 47% and 72% of total CE transferred from HDL, respectively. Moreover, the relative proportion of CE transferred from HDL to VLDL(1) in type 2 diabetes patients increased progressively with increase in plasma TG levels. The VLDL(1) subfraction accounted for 34%, 43%, and 52% of total CE transferred from HDL to TG-rich lipoproteins in patients from G1, G2, and G3, respectively. Finally, dense LDL acquired an average of 45% of total CE transferred from HDL to LDL in type 2 diabetes patients. In conclusion, CETP contributes significantly to the formation of small dense LDL particles in type 2 diabetes by a preferential CE transfer from HDL to small dense LDL, as well as through an indirect mechanism involving an enhanced CE transfer from HDL to VLDL(1), the specific precursors of small dense LDL particles in plasma.
血浆胆固醇酯转运蛋白（CETP）通过促进中性脂质的异质交换来促进血管内脂蛋白重塑。为了确定甘油三酯血症的程度是否会影响2型糖尿病患者动脉粥样硬化性血浆脂蛋白颗粒之间CETP介导的高密度脂蛋白胆固醇酯（HDL CE）的重新分布，我们评估了2型糖尿病患者（n = 38）血浆中CE从HDL向含载脂蛋白B的脂蛋白受体的转移量。同时，我们研究了CE转移与动脉粥样硬化性致密低密度脂蛋白（LDL）谱出现之间的潜在关系。根据空腹血浆甘油三酯（TG）水平，将糖尿病患者分为3个亚组：第1组（G1），TG<100 mg/dL；第2组（G2），100<TG<200 mg/dL；第3组（G3），TG>200 mg/dL。2型糖尿病患者呈现出一种不对称的LDL谱，其中致密LDL亚组分占主导。致密LDL亚组分的血浆水平与血浆甘油三酯（TG）水平呈强正相关（r = 0.471；P = 0.0003）。与G2或G1相比，G3组中CE从HDL向含载脂蛋白B的脂蛋白的转移速率显著提高（G3、G2和G1组中转移的CE量分别为46.2±8.1、33.6±5.3和28.2±2.7 μg CE·h⁻¹·mL⁻¹；G3与G1相比，P<0.0001；G2与G1相比，P = 0.0001；G2与G3相比，P = 0.02）。2型糖尿病亚组之间，极低密度脂蛋白（VLDL）和LDL作为HDL中CE受体的相对能力不同。在G1组中，LDL颗粒是优先的CE受体，占从HDL转移的总CE的74%。相比之下，在G2和G3组中，富含TG的脂蛋白亚组分分别占从HDL转移的总CE的47%和72%。此外，2型糖尿病患者中从HDL转移到VLDL₁的CE相对比例随着血浆TG水平的升高而逐渐增加。在G1、G2和G3组患者中，VLDL₁亚组分分别占从HDL转移到富含TG的脂蛋白的总CE的34%、43%和52%。最后，在2型糖尿病患者中，致密LDL平均获得了从HDL转移到LDL的总CE的45%。总之，CETP通过优先将CE从HDL转移到小而致密的LDL，以及通过一种间接机制（涉及增强CE从HDL转移到VLDL₁，VLDL₁是血浆中小而致密LDL颗粒的特定前体），对2型糖尿病中小而致密LDL颗粒的形成有显著贡献。
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