Brites F D, Cavallero E, de Geitere C, Nicolaïew N, Jacotot B, Rosseneu M, Fruchart J C, Wikinski R L, Castro G R
Departamento de Bioquímica Clínica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Clin Chim Acta. 1999 Jan;279(1-2):1-14. doi: 10.1016/s0009-8981(98)00155-7.
In this study, we first characterized the lipoprotein components of serum samples obtained from a group of well-controlled diabetic patients and from healthy subjects in fasting and postprandial states. We then explored some aspects of reverse cholesterol transport in the same population. Patients showed high levels of fasting triglycerides, postprandial triglyceride responses and LpC-III levels (3.18+/-0.86 vs 2.17+/-0.54 mg/dl, P < 0.001). There were also positive correlations between LpC-III and fasting triglycerides (r = 0.82, P < 0.001), total triglyceride area (r = 0.75, P < 0.001) and incremental triglyceride area (r = 0.54, P < 0.001). HDL-C and apo A-I were significantly decreased in diabetic patients due to a selective reduction in LpA-I subfraction, whose antiatherogenic role is generally accepted (37.4+/-8.0 vs 49.2+/-12.5 mg/dl, P < 0.001). In addition, HDL from patients proved to be triglyceride enriched and cholesteryl ester depleted, alterations which were further amplified in the postprandial state. The molar ratio HDL-C/apo A-I + apo A-II, already defined as a predictor of apo A-I fractional catabolic rate, was significantly diminished in the patient group (15.1+/-2.2 vs 20.8+/-3.3, P < 0.001), thus suggesting an accelerated catabolism of apo A-I. For the first time, we describe here the presence of a small apo A-I-containing particle, isolated by two-dimensional electrophoresis and characterized by immunoblotting, only in samples from diabetic patients. This particle that we named pre-beta0, has an apparent molecular weight of 40 kDa. As regards the capacity of serum samples to promote cholesterol efflux from [3H]cholesterol-labeled Fu5AH rat hepatoma cells, patient samples were found to induce significantly lower cholesterol efflux than controls only in the postprandial state (21.2+/-3.3 vs 23.8+/-1.8%, P = 0.012). The presence of pre-beta0 in samples from diabetic patients might therefore be associated to an altered capacity of these serum samples to promote cellular cholesterol efflux. Overall, these abnormalities may contribute to a delay in the reverse cholesterol transport pathway in type 2 diabetic patients.
在本研究中，我们首先对一组血糖控制良好的糖尿病患者以及健康受试者在空腹和餐后状态下获取的血清样本中的脂蛋白成分进行了表征。然后，我们在同一人群中探讨了胆固醇逆向转运的一些方面。患者的空腹甘油三酯、餐后甘油三酯反应和LpC-III水平较高（3.18±0.86 vs 2.17±0.54 mg/dl，P < 0.001）。LpC-III与空腹甘油三酯（r = 0.82，P < 0.001）、总甘油三酯面积（r = 0.75，P < 0.001）和甘油三酯增量面积（r = 0.54，P < 0.001）之间也存在正相关。糖尿病患者的HDL-C和载脂蛋白A-I显著降低，这是由于LpA-I亚组分选择性减少所致，其抗动脉粥样硬化作用已得到普遍认可（37.4±8.0 vs 49.2±12.5 mg/dl，P < 0.001）。此外，患者的HDL被证明富含甘油三酯且胆固醇酯减少，这些改变在餐后状态下进一步加剧。HDL-C/载脂蛋白A-I + 载脂蛋白A-II的摩尔比，已被定义为载脂蛋白A-I分数分解代谢率的预测指标，在患者组中显著降低（15.1±2.2 vs 20.8±3.3，P < 0.001），因此表明载脂蛋白A-I的分解代谢加速。我们首次在此描述了仅在糖尿病患者样本中存在的一种含载脂蛋白A-I的小颗粒，通过二维电泳分离并用免疫印迹法进行表征。我们将这种颗粒命名为前β0，其表观分子量为40 kDa。关于血清样本促进[3H]胆固醇标记的Fu5AH大鼠肝癌细胞胆固醇流出的能力，仅在餐后状态下发现患者样本诱导的胆固醇流出显著低于对照组（21.2±3.3 vs 23.8±1.8%，P = 0.012）。因此，糖尿病患者样本中前β0的存在可能与这些血清样本促进细胞胆固醇流出的能力改变有关。总体而言，这些异常可能导致2型糖尿病患者胆固醇逆向转运途径延迟。
