Camera M, Mussoni L, Maderna P, Sironi L, Prati L, Colli S, Bernini F, Corsini A, Tremoli E
Institute of Pharmacological Sciences, University of Milan, Italy.
Cytotechnology. 1993;11 Suppl 1:S144-6.
Cultured human umbilical vein endothelial cells (EC) exposed to native and acetylated low density lipoproteins (LDL and acetyl-LDL) show an increased synthesis of PAI-1. Confluent EC monolayers were incubated for 16-18 hours in medium 199 with or without different concentrations of LDL and acetyl-LDL and PAI-1 antigen levels were measured in conditioned medium. LDL and acetyl-LDL increased the release of PAI-1 by EC in a concentration-dependent manner. The effect was specific for PAI-1 because tissue type plasminogen activator (t-PA) and expression of procoagulant activity were not affected by either lipoprotein. The observation that native and acetyl-LDL, which are known to interact with different receptors on EC, exert the same stimulatory effect on PAI-1 release rules out the possibility of an involvement of the LDL receptor in mediating this effect. Experiments carried out incubating native LDL in the presence of a monoclonal antibody against LDL receptor and using binding-defective LDL with a reduced affinity for the LDL receptor (approximately 50% with respect to normal LDL) further excluded an involvement of the classical LDL receptor in mediating the effect of the lipoproteins on PAI-1 synthesis by EC.
暴露于天然和乙酰化低密度脂蛋白（LDL和乙酰化LDL）的培养人脐静脉内皮细胞（EC）显示纤溶酶原激活物抑制因子-1（PAI-1）的合成增加。将汇合的EC单层细胞在含有或不含有不同浓度LDL和乙酰化LDL的199培养基中孵育16 - 18小时，并在条件培养基中测量PAI-1抗原水平。LDL和乙酰化LDL以浓度依赖的方式增加EC释放PAI-1。该作用对PAI-1具有特异性，因为组织型纤溶酶原激活物（t-PA）和促凝活性的表达均不受任何一种脂蛋白的影响。已知天然LDL和乙酰化LDL与EC上不同受体相互作用，但它们对PAI-1释放具有相同的刺激作用，这一观察结果排除了LDL受体介导此效应的可能性。在存在抗LDL受体单克隆抗体的情况下孵育天然LDL以及使用对LDL受体亲和力降低（相对于正常LDL约为50%）的结合缺陷型LDL进行的实验，进一步排除了经典LDL受体介导脂蛋白对EC合成PAI-1的作用。
