Berberian P A, Jenison M W, Roddick V
Exp Mol Pathol. 1985 Aug;43(1):36-55. doi: 10.1016/0014-4800(85)90053-x.
This report validates and expands further the interpretation of our findings on prostaglandins and lysosomes in rabbit aortic homogenates (see paper I of this series) to enzymatically isolated and separated aortic cell populations during atherogenesis. Evidence is provided by which isolated arterial cells may be considered representative of in situ increases of diseased aortic tissue prostaglandin I2 and E2 levels, as well as lysosomal acid hydrolase activities and total cholesterol content based on DNA. Increasing latency of aortic lysosomal N-acetyl-beta-glucosaminidase activity was confirmed and correlated with increasing severity of atherosclerosis, in parallel to increasing levels of prostaglandin I2 but not increasing levels of prostaglandin E2. Ultrastructural observations also confirmed aortic intracellular lipid accumulation within lysosomes and as lipid droplets. Consistent with these relationships, separated low density, lipid-filled aortic cells were especially increased in total (197%) and latent (15%) lysosomal acid hydrolase activities, catalase activity (274%), total cholesterol (151%), and in both prostaglandin I2 (67%) and E2 (325%) levels based on DNA, as compared to control aortic cells or more normal-appearing high-density diseased aortic smooth muscle cells; high-density diseased aortic cells were increased in prostaglandin E2 but similar in latent acid hydrolase activity compared to control aortic cells. Since the total cholesterol content of rabbit atherosclerotic aortas was evidenced more intracellularly (75%) than extracellularly (25%) in this study, the association of increased prostaglandin I2 and E2 levels with low-density lipid-filled cells suggest the participation of these prostaglandins in the genesis of aortic foam cells during arterial lipid accumulation in rabbit atherosclerosis. The association of increasing prostaglandin I2 levels and increasing latent lysosomal N-acetyl-beta-glucosaminidase activities also implicates a possible relationship between this prostaglandin and lysosomal membranes of aortic cells, either primary or secondary to intralysosomal lipid accumulation.
本报告进一步验证并拓展了我们对兔主动脉匀浆中前列腺素和溶酶体研究结果的解读（见本系列论文I），研究对象为动脉粥样硬化形成过程中经酶分离和分选的主动脉细胞群体。研究提供的证据表明，基于DNA，分离出的动脉细胞可被视为病变主动脉组织中前列腺素I2和E2水平、溶酶体酸性水解酶活性及总胆固醇含量原位增加的代表。主动脉溶酶体N - 乙酰 - β - 氨基葡萄糖苷酶活性潜伏期延长得到证实，并与动脉粥样硬化严重程度增加相关，与前列腺素I2水平升高平行，但与前列腺素E2水平升高无关。超微结构观察也证实主动脉细胞内脂质在溶酶体和脂滴中蓄积。与这些关系一致，与对照主动脉细胞或外观更正常的高密度病变主动脉平滑肌细胞相比，分选得到的低密度、充满脂质的主动脉细胞在总溶酶体酸性水解酶活性（197%）和潜伏期活性（15%）、过氧化氢酶活性（274%）、总胆固醇（151%）以及基于DNA的前列腺素I2（67%）和E2（325%）水平方面均有显著增加；高密度病变主动脉细胞的前列腺素E2水平升高，但与对照主动脉细胞相比，潜伏期酸性水解酶活性相似。由于本研究表明兔动脉粥样硬化主动脉的总胆固醇含量更多存在于细胞内（75%）而非细胞外（25%），前列腺素I2和E2水平升高与低密度脂质填充细胞的关联表明这些前列腺素参与了兔动脉粥样硬化动脉脂质蓄积过程中主动脉泡沫细胞的形成。前列腺素I2水平升高与潜伏期溶酶体N - 乙酰 - β - 氨基葡萄糖苷酶活性增加之间的关联还暗示了该前列腺素与主动脉细胞溶酶体膜之间可能存在的关系，这种关系可能是原发性的，也可能是溶酶体内脂质蓄积继发的。
