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Pravastatin inhibits fibrinogen- and FDP-induced inflammatory response via reducing the production of IL-6, TNF-α and iNOS in vascular smooth muscle cells.

Abstract
Atherosclerosis is a chronic inflammatory response of the arterial wall to pro‑atherosclerotic factors. As an inflammatory marker, fibrinogen directly participates in the pathogenesis of atherosclerosis. Our previous study demonstrated that fibrinogen and fibrin degradation products (FDP) produce a pro‑inflammatory effect on vascular smooth muscle cells (VSMCs) through inducing the production of interleukin‑6 (IL‑6), tumor necrosis factor‑α (TNF‑α) and inducible nitric oxide synthase (iNOS). In the present study, the effects of pravastatin on fibrinogen‑ and FDP‑induced expression of IL‑6, TNF‑α and iNOS were observed in VSMCs. The results showed that pravastatin dose‑dependently inhibited fibrinogen‑ and FDP‑stimulated expression of IL‑6, TNF‑α and iNOS in VSMCs at the mRNA and protein level. The maximal inhibition of protein expression of IL‑6, TNF‑α and iNOS was 46.9, 42.7 and 49.2% in fibrinogen‑stimulated VSMCs, and 50.2, 49.8 and 53.6% in FDP‑stimulated VSMCs, respectively. This suggests that pravastatin has the ability to relieve vascular inflammation via inhibiting the generation of IL‑6, TNF‑α and iNOS. The results of the present study may aid in further explaining the beneficial effects of pravastatin on atherosclerosis and related cardiovascular diseases. In addition, they suggest that application of pravastatin may be beneficial for prevention of atherosclerosis formation in hyperfibrinogenemia.
AuthorsPeipei Lu, Juntian Liu, Xiaoming Pang
JournalMolecular medicine reports (Mol Med Rep) Vol. 12 Issue 4 Pg. 6145-51 (Oct 2015) ISSN: 1791-3004 [Electronic] Greece
PMID26238934 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Fibrin Fibrinogen Degradation Products
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Fibrinogen
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Pravastatin
Topics
  • Animals
  • Atherosclerosis (drug therapy)
  • Cell Line
  • Dose-Response Relationship, Drug
  • Fibrin Fibrinogen Degradation Products (adverse effects)
  • Fibrinogen (adverse effects)
  • Inflammation (pathology)
  • Interleukin-6 (genetics, metabolism)
  • Muscle, Smooth, Vascular (cytology)
  • Myocytes, Smooth Muscle (cytology, drug effects)
  • Nitric Oxide Synthase Type II (genetics, metabolism)
  • Pravastatin (pharmacology)
  • Rats, Sprague-Dawley
  • Tumor Necrosis Factor-alpha (genetics, metabolism)

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