Pro-inflammatory effect of fibrinogen on vascular smooth muscle cells by regulating the expression of PPARα, PPARγ and MMP-9

Wang,Shuyue; Liu,Juntian; Wu,Di; Pang,Xiaoming; Zhao,Jingjing; Zhang,Xiaolu

doi:10.3892/br.2015.459

Pro-inflammatory effect of fibrinogen on vascular smooth muscle cells by regulating the expression of PPARα, PPARγ and MMP-9

Authors:
- Shuyue Wang
- Juntian Liu
- Di Wu
- Xiaoming Pang
- Jingjing Zhao
- Xiaolu Zhang
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Affiliations: Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, P.R. China
Published online on: May 4, 2015 https://doi.org/10.3892/br.2015.459
Pages: 513-518

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Abstract

Atherosclerosis is a chronic inﬂammatory disease in the vessel. As one of the inﬂammatory markers, ﬁbrinogen has been indicated in formation and progression of atherosclerosis. However, it is completely unclear whether fibrinogen produces a pro‑inﬂammatory effect on vascular smooth muscle cells (VSMCs). The purpose of the present study was to observe the effect of ﬁbrinogen on the expression of peroxisome proliferator‑activated receptors‑α (PPARα), PPARγ and matrix metalloproteinase‑9 (MMP‑9) in VSMCs. Rat VSMCs were cultured and ﬁbrinogen was used as a stimulant for PPARα, PPARγ and MMP‑9 expression. mRNA expression of PPARα, PPARγ and MMP‑9 was identiﬁed with the reverse transcription polymerase chain reaction. Protein production of PPARα and PPARγ was examined by western blot analysis and the MMP‑9 level in the supernatant of VSMCs was measured with the enzyme‑linked immunosorbent assay. The results showed that fibrinogen downregulated mRNA and protein expression of PPARα and PPARγ, and upregulated mRNA and protein generation of MMP‑9 in VSMCs in time‑ and concentration‑dependent manners. The maximal inhibition of protein expression of PPARα and PPARγ was 71.8 and 79.9%, respectively. The maximal release of MMP‑9 was 4 times over the control. The results suggest that fibrinogen exerts a pro‑inﬂammatory effect on VSMCs through inhibiting the expression of anti‑inflammatory cytokine PPARα and PPARγ and stimulating the production of pro‑inflammatory cytokine MMP‑9. The ﬁndings provide new evidence for the pro‑inﬂammatory and pro‑atherosclerotic effects of ﬁbrinogen.

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