Sironi L, Mussoni L, Prati L, Baldassarre D, Camera M, Banfi C, Tremoli E
Institute of Pharmacological Sciences and E. Grossi Paoletti Center, University of Milan, Italy.
Arterioscler Thromb Vasc Biol. 1996 Jan;16(1):89-96. doi: 10.1161/01.atv.16.1.89.
The effect of VLDL on plasminogen activator inhibitor type 1 biosynthesis in HepG2 cells was investigated. Exposure of HepG2 cells to VLDL (range, 10 to 100 micrograms protein per milliliter) for 16 hours resulted in an enhanced release of PAI-1 antigen and PAI activity into conditioned medium, accompanied by the accumulation of intracellular triglycerides. By using a monoclonal antibody (IgG C7) specific to the LDL receptor, we showed that the effect of VLDL is mediated by its interaction with the LDL receptor. Enhanced PAI-1 release was due to increased biosynthesis: PAI-1 mRNA was doubled, mainly because of the effect on the 2.2-kb PAI-1 mRNA rather than the 3.2-kb transcript. Addition of insulin with the VLDL further enhanced PAI-1 antigen release and PAI-1 mRNA accumulation. The effect of VLDL on steady state levels of PAI-1 mRNA was apparently not due to an increase of gene transcription but to stabilization of both PAI-1 mRNA transcripts. The enhancing effect of VLDL on PAI-1 biosynthesis in HepG2 cells may raise PAI-1 antigen levels not only in hypertriglyceridemic states but also in those conditions in which both insulin and VLDL are elevated.
研究了极低密度脂蛋白（VLDL）对HepG2细胞中纤溶酶原激活物抑制剂1（PAI-1）生物合成的影响。将HepG2细胞暴露于VLDL（浓度范围为每毫升10至100微克蛋白质）16小时，导致PAI-1抗原和PAI活性向条件培养基中的释放增加，同时伴有细胞内甘油三酯的积累。通过使用针对低密度脂蛋白（LDL）受体的单克隆抗体（IgG C7），我们表明VLDL的作用是通过其与LDL受体的相互作用介导的。PAI-1释放增加是由于生物合成增加：PAI-1 mRNA增加了一倍，主要是因为对2.2-kb PAI-1 mRNA的影响，而不是对3.2-kb转录本的影响。VLDL与胰岛素一起添加进一步增强了PAI-1抗原释放和PAI-1 mRNA积累。VLDL对PAI-1 mRNA稳态水平的影响显然不是由于基因转录增加，而是由于两种PAI-1 mRNA转录本的稳定。VLDL对HepG2细胞中PAI-1生物合成的增强作用可能不仅在高甘油三酯血症状态下，而且在胰岛素和VLDL均升高的情况下提高PAI-1抗原水平。
