Pro-inflammatory effect of fibrinogen on vascular smooth muscle cells by regulating the expression of PPAR alpha, PPAR gamma and MMP-9

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-alpha (PPAR alpha), PPAR gamma and matrix metalloproteinase-9 (MMP-9) in VSMCs. Rat VSMCs were cultured and fibrinogen was used as a stimulant for PPAR alpha, PPAR gamma and MMP-9 expression. mRNA expression of PPAR alpha, PPAR gamma and MMP-9 was identified with the reverse transcription polymerase chain reaction. Protein production of PPAR alpha and PPAR gamma 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 PPAR alpha and PPAR gamma, and upregulated mRNA and protein generation of MMP-9 in VSMCs in time- and concentration-dependent manners. The maximal inhibition of protein expression of PPAR alpha and PPAR gamma 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 PPAR alpha and PPAR gamma 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.