Salisbury B G, Falcone D J, Minick C R
Am J Pathol. 1985 Jul;120(1):6-11.
The interaction of arterial proteoglycans (PGs) and low-density lipoproteins (LDLs) has been postulated to be an important factor in extracellular cholesterol accumulation in the arterial wall. In the present study, insoluble complexes of LDL and PG (LDL-PG) were prepared and their effects on cholesteryl ester accumulation in mouse peritoneal macrophages was tested. The cholesteryl ester content of macrophages incubated with LDL-PG for 3 days was greater than 20 times that observed in cells incubated with LDL alone. The uptake of 125I-LDL by macrophages was markedly stimulated if LDL was incorporated into a complex with PG. However, in contrast to either LDL or acetylated LDL (ALDL), the extent of subsequent degradation of LDL-PG by the cells was reduced. The uptake and degradation of LDL-PG complexes stimulated macrophage incorporation of 14C-oleic acid into cholesteryl oleate 4- to 5-fold over LDL alone; however, esterification was significantly less than that observed with ALDL, even though more LDL-PG was degraded. Ultrastructurally, macrophages incubated with LDL-PG complexes contained lipid droplets as well as numerous phagocytic vacuoles often containing material similar in appearance to insoluble complexes. These results demonstrate that components of the extracellular matrix, such as PG, can modify the catabolism of LDL by scavenger cells. This phenomenon may be potentially important with respect to foam-cell genesis from macrophages in the arterial wall.
动脉蛋白聚糖（PGs）与低密度脂蛋白（LDLs）的相互作用被认为是动脉壁细胞外胆固醇蓄积的一个重要因素。在本研究中，制备了LDL与PG的不溶性复合物（LDL-PG），并测试了它们对小鼠腹腔巨噬细胞胆固醇酯蓄积的影响。用LDL-PG孵育3天的巨噬细胞的胆固醇酯含量比仅用LDL孵育的细胞中观察到的含量高20倍以上。如果LDL与PG形成复合物，巨噬细胞对125I-LDL的摄取会受到明显刺激。然而，与LDL或乙酰化LDL（ALDL）不同，细胞随后对LDL-PG的降解程度降低。LDL-PG复合物的摄取和降解刺激巨噬细胞将14C-油酸掺入胆固醇油酸酯的量比仅用LDL时高4至5倍；然而，尽管更多的LDL-PG被降解，但酯化程度明显低于用ALDL时观察到的程度。在超微结构上，用LDL-PG复合物孵育的巨噬细胞含有脂滴以及许多吞噬泡，吞噬泡中常常含有外观与不溶性复合物相似的物质。这些结果表明，细胞外基质的成分，如PG，可以改变吞噬细胞对LDL的分解代谢。就动脉壁巨噬细胞产生泡沫细胞而言，这种现象可能具有潜在的重要性。
