Article Text


Basic science: Cardiovascular disease basic research
e0147 Mechanism of different activators of PPARαregulating plasminogen activator inhibitor-1 expression
  1. Chen Jing1,
  2. Ye Ping2,
  3. Ren Xiangqun1,
  4. Ding Jun1,
  5. Huang Tongrui1,
  6. Wang Chengzhang1
  1. 1Chinese Pla Peacehospital
  2. 2Chinese Pla General Hospital


Objective To observe the effects of fenofibrate and linoleic acid which was the different activators of PPARα on the expression of PAI-1 and PPARα in HepG2 cells. To investigate the relationship and mechanisms between the promoter and expression of PAI-1 that how the fenofibrate and linoleic acid to act on PAI-1. And to observe if PPARα involved in this procession.

Methods HepG2 cells were exposed to fenofibrate and linoleic acid in varying concentrations, RT-PCR was used to determine the mRNA expression of PAI-1 and PPARα. Several luciferase reporter gene recombinant plasmid containing different length sequences of human PAI-1 gene promoter from −804 to +17bp were constructed and transiently transfected into HepG2 cells. At the same time, co-transfected with PPARα-pSG5 expression plasmid, then different stimulating factors were added to induce the transfected cells. Transcriptional activity of PAI-1 was demonstrated by the measure of luciferase activity.

Results 1. Fenofibrate could remarkably decreased PAI-1 mRNA expression in HepG2 cells (p<0.05 or p<0.01), but linoleic acid could significant increased PAI-1 mRNA level (p<0.05 or p<0.01), and they were all in a concentration-dependent manner. 2. Fenofibrate and linoleic acid could raise the mRNA level of PPARα (p<0.05 or p<0.01), which were also in a concentration-dependent way. 3. The PAI-1 transcriptional activity were significantly suppressed by fenofibrate (p<0.05), but induced by linoleic acid (p<0.01) in HepG2 cells transfected with PAI-pGL3 total length promoter constructs. 4. When co-transfected with PPARα-pSG5, fenofibrate could suppress the level of PAI-1 transcription further more (p<0.05), while increased y linoleic acid (p<0.01). 5. The PAI-1 transcriptional activity were very inconsistent when transfected with the plasmid containing different length sequences of human PAI-1 gene promoter from −804 to +17 bp.

Conclusions Fenofibrate and linoleic acid could increase the mRNA level of PPARα, and they regulate the synthesis of PAI-1 from transcriptional level, which was concerned with the activated of PPARα by Fenofibrate and linoleic acid. The sequences that could regulate the expression of PAI-1 gene induced by fenofibrate might exist in the areas from −804 to −636 and −636 to −449 of PAI-1 promoter and existed in the areas rom −804 to −636 and −449 to −276 induced by linoleic acid. The effects on expression of PAI-1 were very inconsistently, so there might be other mechanisms involved.

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