Tan C E, Foster L, Caslake M J, Bedford D, Watson T D, McConnell M, Packard C J, Shepherd J
Department of Pathological Biochemistry, University of Glasgow, Glasgow Royal Infirmary, UK.
Arterioscler Thromb Vasc Biol. 1995 Nov;15(11):1839-48. doi: 10.1161/01.atv.15.11.1839.
VLDL1, VLDL2, IDL, and LDL and its subfractions (LDL-I, LDL-II, and LDL-III) were quantified in 304 normolipemic subjects together with postheparin plasma lipase activities, waist/hip ratio, fasting insulin, and glucose. Concentrations of VLDL1 and VLDL2 rose as plasma triglycerides (TGs) increased across the normal range, but the association of plasma TGs with VLDL1 showed a steeper slope than that of VLDL2 (P < .001). Plasma TG level was the most important determination of LDL subfraction distribution. The least dense species, LDL-I, decreased as the level of this plasma lipid rose in the population. LDL-II in both men and women exhibited a positive association with plasma TG level in the range 0.5 to 1.3 mmol/L, increasing from about 100 to 200 mg/dL. In contrast, within this TG range the LDL-III concentration was low (approximately equal to 30 mg/dL) and changed little. As plasma TGs rose from 1.3 to 3.0 mmol/L there was a significant fall in LDL-II concentration in men (r = .45, P < .001) but not in women (r = .1, NS). Conversely, above the TG threshold of 1.3 mmol/L there was a steeper rise in LDL-III concentrations in men than in women (P < .001); 42% of the men had and LDL-III in the range associated with high risk of heart disease ( > 100 mg lipoprotein/dL plasma) compared with only 17% of the women. Other influences on the LDL subfraction profile were the activities of lipases and parameters indicative of the presence of insulin resistance. Men on average had twice the hepatic lipase activity of women. This enzyme was not strongly associated with variation in the LDL subfraction profile in men, but in women it was correlated with LDL-III (r = 39, P = .001) and remained a significant predictor in multivariate analysis. Increased waist/hip ratio, fasting insulin, and glucose were correlated negatively with LDL-I and positively with LDL-III, primarily, at least in the case of LDL-III, through raising plasma TGs. On the basis of these cross-sectional observations we postulate the following model for the generation of LDL-III. Subjects develop elevated levels of large TG-rich VLDL1 for a number of reasons, including failure of insulin action. The increase in the concentration of VLDL1 expands the plasma TG pool, and this, via the action of cholesteryl ester transfer protein (which facilitates neutral lipid exchange between lipoprotein particles), promotes the net transfer of TGs into LDL-II, the major LDL species.(ABSTRACT TRUNCATED AT 400 WORDS)
在304名血脂正常的受试者中，对极低密度脂蛋白1（VLDL1）、极低密度脂蛋白2（VLDL2）、中间密度脂蛋白（IDL）、低密度脂蛋白（LDL）及其亚组分（LDL-I、LDL-II和LDL-III）进行了定量分析，并同时检测了肝素后血浆脂肪酶活性、腰臀比、空腹胰岛素和血糖。随着血浆甘油三酯（TGs）在正常范围内升高，VLDL1和VLDL2的浓度也随之升高，但血浆TGs与VLDL1的关联斜率比与VLDL2的更陡（P < 0.001）。血浆TG水平是LDL亚组分分布的最重要决定因素。密度最低的组分LDL-I，随着人群中这种血浆脂质水平的升高而降低。男性和女性的LDL-II在0.5至1.3 mmol/L范围内与血浆TG水平呈正相关，从约100 mg/dL增加到200 mg/dL。相比之下，在此TG范围内，LDL-III浓度较低（约等于30 mg/dL）且变化不大。当血浆TGs从1.3 mmol/L升至3.0 mmol/L时，男性的LDL-II浓度显著下降（r = 0.45，P < 0.001），而女性则无明显变化（r = 0.1，无显著性差异）。相反，在TG阈值1.3 mmol/L以上，男性LDL-III浓度的上升比女性更陡（P < 0.001）；42%的男性LDL-III处于与心脏病高风险相关的范围内（> 100 mg脂蛋白/dL血浆），而女性只有17%。对LDL亚组分谱的其他影响因素是脂肪酶活性和提示胰岛素抵抗存在的参数。男性的肝脂肪酶活性平均是女性的两倍。这种酶与男性LDL亚组分谱的变化没有很强的关联，但在女性中它与LDL-III相关（r = 0.39，P = 0.001），并且在多变量分析中仍然是一个显著的预测因子。腰臀比、空腹胰岛素和血糖升高与LDL-I呈负相关，与LDL-III呈正相关，主要是通过升高血浆TGs，至少在LDL-III的情况下是这样。基于这些横断面观察结果，我们提出了以下LDL-III生成模型。由于多种原因，包括胰岛素作用失效，受试者体内富含TG的大颗粒VLDL1水平升高。VLDL1浓度的增加扩大了血浆TG池，并且通过胆固醇酯转移蛋白的作用（促进脂蛋白颗粒之间的中性脂质交换），促进TGs向LDL-II（主要的LDL组分）的净转移。（摘要截短至400字）
