Musanti R, Chiari A, Ghiselli G
Farmitalia Carlo Erba Research Institute, Milan, Italy.
Arterioscler Thromb. 1991 Jul-Aug;11(4):1111-9. doi: 10.1161/01.atv.11.4.1111.
Cholesterol accumulation in macrophages that have migrated in the subintimal space leads to foam cell formation, which is believed to be one of the initiating events in atherosclerosis. In this study we investigated the effect of cholesterol feeding on peritoneal monocyte/macrophage cholesterol content and peritoneal cavity lipoprotein composition in rats. A cholesterol (2%) and cholic acid (1%) diet caused significant hypercholesterolemia in plasma, and at the same time the cholesterol content of peritoneal monocytes/macrophages was increased. At day 7, the cellular cholesteryl ester content had risen to 30.1 micrograms/mg cellular protein from a baseline value of 9.2 micrograms/mg. The unesterified cholesterol content also increased by 56%. At this time, acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity was doubled, whereas neutral and acidic cholesteryl ester hydrolase activities were unchanged. Reversal to the regular chow diet after 7 days of the cholesterol-enriched diet normalized plasma cholesterol levels as well as peritoneal monocyte/macrophage cholesteryl ester content. ACAT activity also decreased toward normal levels. Analysis of the d less than 1.21 g/ml peritoneal lipoproteins isolated by ultracentrifugation revealed the presence, in both normal and hypercholesterolemic rats, of apolipoprotein A-I-rich lipid complexes with pre-beta mobility on agarose gel electrophoresis. The size of the peritoneal lipoproteins was smaller than that of plasmatic high density lipoproteins, and their chemical composition was also different from that of the major plasma lipoproteins. The cholesteryl ester content of peritoneal lipoproteins increased after feeding of the cholesterol-enriched diet. In conclusion, our results show that cholesterol feeding leads to rapid accumulation of cholesteryl esters in monocytes/macrophages. As soon as plasma cholesterol levels are returned to normal, cellular cholesterol content is also normalized.(ABSTRACT TRUNCATED AT 250 WORDS)
迁移至内膜下间隙的巨噬细胞中胆固醇蓄积会导致泡沫细胞形成，这被认为是动脉粥样硬化的起始事件之一。在本研究中，我们调查了喂食胆固醇对大鼠腹膜单核细胞/巨噬细胞胆固醇含量及腹膜腔脂蛋白组成的影响。含2%胆固醇和1%胆酸的饮食导致血浆中显著的高胆固醇血症，同时腹膜单核细胞/巨噬细胞的胆固醇含量增加。在第7天，细胞胆固醇酯含量从基线值9.2微克/毫克细胞蛋白升至30.1微克/毫克。未酯化胆固醇含量也增加了56%。此时，酰基辅酶A：胆固醇酰基转移酶（ACAT）活性加倍，而中性和酸性胆固醇酯水解酶活性未变。富含胆固醇的饮食7天后恢复至常规饲料饮食，使血浆胆固醇水平以及腹膜单核细胞/巨噬细胞胆固醇酯含量恢复正常。ACAT活性也降至正常水平。对通过超速离心分离的密度小于1.21克/毫升的腹膜脂蛋白进行分析发现，在正常和高胆固醇血症大鼠中，均存在富含载脂蛋白A-I的脂质复合物，在琼脂糖凝胶电泳上具有前β迁移率。腹膜脂蛋白的大小小于血浆高密度脂蛋白，其化学组成也与主要血浆脂蛋白不同。喂食富含胆固醇的饮食后，腹膜脂蛋白的胆固醇酯含量增加。总之，我们的结果表明，喂食胆固醇会导致单核细胞/巨噬细胞中胆固醇酯快速蓄积。一旦血浆胆固醇水平恢复正常，细胞胆固醇含量也会恢复正常。（摘要截短至250字）
