title: Pro-inflammatory effect of fibrinogen and FDP on vascular smooth muscle cells by IL-6, TNF-α and iNOS.
abstract: OBJECTIVE
  Atherosclerosis is a chronic inflammatory response of the arterial wall to multiple endothelial injuries. As one of the inflammatory markers, fibrinogen has been implicated in pathogenesis of atherosclerosis. But, it is not completely understood whether atherogenesis of fibrinogen is related to its pro-inflammatory effect on vascular smooth muscle cells (VSMCs). The purpose of the present study was to observe effects of fibrinogen and fibrin degradation products (FDP) on interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and inducible nitric oxide synthase (iNOS) generation in rat VSMCs.
  
  
  METHODS
  Rat VSMCs were cultured, and fibrinogen and FDP were used as stimulants for IL-6, TNF-α, and iNOS. IL-6 and TNF-α level in the supernatant were measured by ELISA, mRNA expression of IL-6, TNF-α, and iNOS were assayed with RT-PCR, and protein expression of iNOS was detected with western blot and immunocytochemistry.
  
  
  RESULTS
  Fibrinogen and FDP both significantly stimulated mRNA and protein expressions of IL-6, TNF-α and iNOS in VSMCs in time- and concentration-dependent ways. The pro-inflammatory potency of FDP is higher than fibrinogen, which seems to mean that smaller fragments of the protein have greater pro-inflammatory activity. Fibrinogen and FDP promote more protein expressions of IL-6 and TNF-α compared to iNOS, suggesting that fibrinogen and FDP produce a pro-inflammatory effect on VSMCs mainly by IL-6 and TNF-α.
  
  
  CONCLUSIONS
  These findings are helpful to better understand pro-inflammatory effect of fibrinogen on VSMCs involved in atherogenesis, and imply a therapeutic strategy targeting hyperfibrinogenemia in atherosclerosis.
authors: Department of Pharmacology, Xi'an Jiaotong University School of Medicine, PR China.
authors: Pei-pei
authors: PP
authors: Lu
authors: Jun-tian
authors: JT
authors: Liu
authors: Na
authors: N
authors: Liu
authors: Fang
authors: F
authors: Guo
authors: Yuan-yuan
authors: YY
authors: Ji
authors: Xiaoming
authors: X
authors: Pang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005338:Fibrin Fibrinogen Degradation Products / Q000502:physiology*; D005340:Fibrinogen / Q000502:physiology*; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology*; D015850:Interleukin-6 / Q000502:physiology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D018836:Inflammation Mediators; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D005340:Fibrinogen; D052247:Nitric Oxide Synthase Type II