Figure 3. Therapeutic anticoagulation with warfarin does not protect against fibrosis.

(A) Mouse plasma international normalized ratios (INRs) after treatment with warfarin or vehicle for 2 weeks. (B and C) Measurement of lung extravascular D-dimer content (B) and total lung hydroxyproline content (C) at day 14 in control mice and mice challenged with bleomycin + FTY720 and treated with vehicle (Veh) or warfarin (War) (hydroxyproline data are representative of 11 independent experiments). (D) Correlation between total lung hydroxyproline content and total lung D-dimer content in mice challenged with bleomycin + FTY720 and treated with warfarin versus vehicle. (E–G) Western blot analyses for cleaved (activated) PAR1 in whole-lung homogenates at day 14 in control mice and mice challenged with bleomycin + FTY720 and treated with dabigatran (Dabi) versus vehicle (E, top panel; densitometry in F) or warfarin versus vehicle (E, bottom panel; densitometry in G). Western blot bands for cleaved PAR1 and GAPDH were seen at the expected molecular weights of ~46 kDa and ~37 kDa, respectively. Western blot data are representative of at least 2 independent experiments for each analysis. Individual data points are presented in graphs, along with mean ± SEM where applicable. *P < 0.05, **P < 0.005 by 2-tailed t tests for indicated pairwise comparisons.