title: Pro-inflammatory effect of fibrinogen on vascular smooth muscle cells by regulating the expression ofPPARα,PPARγ andMMP-9.
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 ofPPARα, PPARγandMMP-9was 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.
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Shuyue
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Juntian
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: D I
authors.initials: DI
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Pang
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Zhang
keywords: MMP-9; PPARα; PPARγ; atherosclerosis; fibrinogen; inflammation; vascular smooth muscle cells