LDL-INDUCED CYTOTOXICITY AND ITS INHIBITION BY HDL IN HUMAN VASCULAR SMOOTH-MUSCLE AND ENDOTHELIAL-CELLS IN CULTURE
LDL-INDUCED CYTOTOXICITY AND ITS INHIBITION BY HDL IN HUMAN VASCULAR SMOOTH-MUSCLE AND ENDOTHELIAL-CELLS IN CULTURE
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DOI：
10.1016/0021-9150(79)90166-7
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发表时间：
1979-01-01
期刊：
影响因子：
5.3
通讯作者：
CHISOLM, GM
中科院分区：
文献类型：
--
作者：
HESSLER, JR;ROBERTSON, AL;CHISOLM, GM
将培养的人主动脉内侧平滑肌细胞（SMC）和脐静脉内皮细胞（EC）暴露于不同浓度的血浆低密度（LDL）和高密度（HDL）脂蛋白中，以评估其对细胞生长的影响。在含有脂蛋白缺乏血清（LPDS, lipoprotein depleted serum, d）的培养基中添加脂蛋白，在蛋白质浓度为4.5 mg/ml的培养基中[剂量]> 1.25 g/ml)，以便单独或联合评价每种脂蛋白的作用。胆固醇浓度为160 .mu时LDL的添加量。g/ml培养基中，与lpd对照和起始细胞数相比，暴露后3天内每皿SMC和EC细胞数量显著减少（SMC P < 0.001; EC P < 0.01）。细胞毒性现象与剂量有关，且仅与LDL胆固醇浓度有关。50 .mu。G /ml未见明显变化。所有测试浓度的HDL都没有产生有害影响。DNA合成的放射自显影评估证实了这一发现。在连续暴露于3h -胸苷48小时后，ldl处理组的标记指数达到了更低的平台。添加HDL可抑制LDL诱导的细胞毒性，但仅在低LDL浓度（100 .mu）时有效。g LDL胆固醇/ml培养基)可以完全阻止HDL的毒性作用。当LDL浓度较高时(250 .mu。g/ml培养基)添加HDL达到HDL/LDL的统一比例也不能阻止LDL诱导的作用。当将LDL添加到脂质缺失血清（LDS为4.5 mg蛋白/ml培养基，通过醚提取除磷脂外的所有脂质制备）而不是LDS时，仅注意到轻微的生长抑制。HDL（和LDS）对LDL毒性的保护可能涉及蛋白质和磷脂成分。
Human aortic medial smooth muscle cells (SMC) and umbilical vein endothelial cells (EC) in culture were exposed to various concentrations of plasma low density (LDL) and high density (HDL) lipoproteins prepared from normolipemic donors to assess their effects on cell growth. So that the effects of each lipoprotein could be evaluated separately and in combination, lipoproteins were added to culture medium containing lipoprotein deficient serum (LPDS, lipoprotein depleted serum (d) [dose] > 1.25 g/ml at a protein concentration of 4.5 mg/ml of medium). The addition of LDL at cholesterol concentrations of 160 .mu.g/ml of culture medium, resulted in significant reductions in the number of SMC and EC cells per dish within 3 days of exposure (P < 0.001, SMC; P < 0.01, EC), when compared with LPDS controls and with the starting cell numbers. The cytotoxic phenomenon was dose-related, and with only LDL cholesterol concentrations .ltoreq. 50 .mu.g/ml no marked changes were seen. HDL at all concentrations tested produced no deleterious effects. Autoradiographic assessment of DNA synthesis confirmed the findings. After 48 h of continuous exposure to 3H-thymidine, labeling indexes reached much lower plateaus in the LDL-treated groups. The addition of HDL inhibited this LDL-induced cytotoxicity, but, only at a low LDL concentration (100 .mu.g LDL cholesterol/ml of medium) could HDL completely prevent toxicity. At the higher LDL concentration tested (250 .mu.g/ml of medium) the addition of HDL up to an HDL/LDL ratio of unity could not prevent the LDL-induced effects. When LDL was added to lipid depleted serum (LDS at 4.5 mg protein/ml culture medium, prepared by ether extraction of all lipids, with the exception of phospholipids) instead of LPDS, only slight growth inhibition was noted. Protection against LDL toxicity by HDL (and LDS) may involve protein and phospholipid components.