Nanjee M N, Cooke C J, Olszewski W L, Miller N E
Department of Cardiovascular Biochemistry, St Bartholomew's and the Royal London School of Medicine and Dentistry, London, UK.
Arterioscler Thromb Vasc Biol. 2000 Sep;20(9):2148-55. doi: 10.1161/01.atv.20.9.2148.
When cultured cells are exposed to plasma, the initial acceptors of unesterified cholesterol are small lipid-poor apolipoprotein A-I (apoA-I)-containing high density lipoproteins (HDLs) with pre-beta electrophoretic mobility. These are converted by lecithin:cholesterol acyltransferase into larger spheroidal cholesteryl ester-rich HDLs with alpha mobility. To study the determinants of the concentration of small pre-beta HDLs in tissue fluids, we collected prenodal peripheral lymph from 34 fasted normal men. By crossed immunoelectrophoresis, the concentration of pre-beta HDLs in lymph averaged 20% of that in plasma. On multiple regression analysis, pre-beta apoA-I concentration in lymph was directly related to pre-beta apoA-I concentration in plasma and independently to alpha apoA-I concentration in lymph. Similar results were obtained when the same apoA-I-containing particles were quantified by size exclusion chromatography. Lymph pre-beta apoA-I concentration was low in a subject with familial lecithin:cholesterol acyltransferase deficiency, despite a normal plasma pre-beta apoA-I concentration, but was normal in a subject with familial lipoprotein lipase deficiency. These results suggest that the concentration of small pre-beta HDLs in human tissue fluids is determined only in part by the transfer of pre-beta HDLs across capillary endothelium from plasma. Local production, by remodeling of spheroidal alpha HDLs in tissue fluids, may be equally important. Lipolysis of triglyceride-rich lipoproteins by lipoprotein lipase appears to have little effect.
当培养的细胞暴露于血浆时,未酯化胆固醇的初始受体是具有前β电泳迁移率的、含少量脂质的载脂蛋白A-I(apoA-I)的高密度脂蛋白(HDL)。这些HDL通过卵磷脂:胆固醇酰基转移酶转化为具有α迁移率的、更大的富含胆固醇酯的球状HDL。为了研究组织液中小的前β HDL浓度的决定因素,我们收集了34名禁食正常男性的结前外周淋巴。通过交叉免疫电泳,淋巴中前β HDL的浓度平均为血浆中的20%。多元回归分析显示,淋巴中前β apoA-I的浓度与血浆中前β apoA-I的浓度直接相关,且与淋巴中α apoA-I的浓度独立相关。当通过尺寸排阻色谱法对相同的含apoA-I颗粒进行定量时,也得到了类似的结果。在一名患有家族性卵磷脂:胆固醇酰基转移酶缺乏症的受试者中,尽管血浆前β apoA-I浓度正常,但淋巴前β apoA-I浓度较低,而在一名患有家族性脂蛋白脂肪酶缺乏症的受试者中,淋巴前β apoA-I浓度正常。这些结果表明,人体组织液中小的前β HDL的浓度仅部分由血浆中前β HDL跨毛细血管内皮的转运决定。通过组织液中球状α HDL的重塑进行的局部产生可能同样重要。脂蛋白脂肪酶对富含甘油三酯的脂蛋白的脂解作用似乎影响不大。