Ragab M S, Selvaraj P, Sgoutas D S
Department of Pathology and Laboratory Medicine, School of Medicine, Emory University Hospital, Atlanta, GA 30322, USA.
Atherosclerosis. 1996 Jun;123(1-2):103-13. doi: 10.1016/0021-9150(95)05790-0.
Because of structural similarities between low density lipoproteins (LDL) and lipoprotein (a) (Lp(a)), we have investigated the properties and the functional activities of oxidized Lp(a) and focused on whether oxidized Lp(a), like oxidized LDL, can induce monocyte differentiation and adhesion of monocytic cells to endothelial cells grown in culture. Oxidized Lp(a), prepared in vitro by cupric ion oxidation, gave absorption curves of conjugated dienes with a lag-phase of 61.7 +/- 6.6 min (mean +/- S.D.) as compared to 85.2 +/- 7.2 min (n = 6, P < 0.01) for oxidized LDL from the same donors and at equimolar concentrations. Degradation of oxidized 125I Lp(a) by the monocytic cell line U937 at 37 degrees C was 1.6 +/- 0.3 nmol/g of cell protein, significantly (P < 0.01) greater than the degradation of oxidized 125I-LDL, which was 1.15 +/- 0.2 nmol/g of cell protein. Equimolar concentrations of oxidized Lp(a) and LDL inhibited the growth of U937 by 82 +/- 8.2% and 64 +/- 7.1%, respectively, when compared with the effect (negligible) produced by native Lp(a) and LDL. In addition, equimolar concentrations of oxidized Lp(a) and LDL induced adhesion molecule, Mac-1 (CD 11b), expression in U937 by 64 +/- 7.1% and 58 +/- 6.1% (P > 0.05), respectively, of the effect produced by phorbol esters (PMA) (P < 0.01). U937 cells incubated with oxidized Lp(a) and LDL, showed an adherence to cultured endothelial cells at 42 +/- 5.2% and 34 +/- 4.8%, respectively (P < 0.05), of the adherence shown by the same cells activated by PMA (P < 0.01). Our results suggest that oxidized Lp(a) like oxidized LDL plays an important role in the development of atherogenesis by inducing adhesion of monocytes to the arterial intimal and by stimulating intimal monocytes to differentiate into macrophages.
由于低密度脂蛋白（LDL）和脂蛋白（a）[Lp（a）]在结构上存在相似性，我们研究了氧化型Lp（a）的性质和功能活性，并着重关注氧化型Lp（a）是否像氧化型LDL一样，能够诱导单核细胞分化以及单核细胞与培养的内皮细胞黏附。通过铜离子氧化体外制备的氧化型Lp（a），其共轭二烯的吸收曲线滞后相为61.7±6.6分钟（平均值±标准差），而来自相同供体且等摩尔浓度的氧化型LDL的滞后相为85.2±7.2分钟（n = 6，P < 0.01）。单核细胞系U937在37℃下对氧化型125I-Lp（a）的降解为1.6±0.3 nmol/g细胞蛋白，显著高于（P < 0.01）氧化型125I-LDL的降解，后者为1.15±0.2 nmol/g细胞蛋白。与天然Lp（a）和LDL产生的影响（可忽略不计）相比，等摩尔浓度的氧化型Lp（a）和LDL分别使U937的生长抑制了82±8.2%和64±7.1%。此外，等摩尔浓度的氧化型Lp（a）和LDL分别使U937中黏附分子Mac-1（CD 11b）的表达达到佛波酯（PMA）产生效应的64±7.1%和58±6.1%（P > 0.05）（P < 0.01）。用氧化型Lp（a）和LDL孵育的U937细胞，分别以PMA激活的相同细胞所显示黏附的42±5.2%和34±4.8%的比例黏附于培养的内皮细胞（P < 0.05）（P < 0.01）。我们的结果表明，氧化型Lp（a）与氧化型LDL一样，通过诱导单核细胞黏附于动脉内膜以及刺激内膜单核细胞分化为巨噬细胞，在动脉粥样硬化的发展过程中起重要作用。
