Pulmonary fibrosis is increased in mice carrying the factor V Leiden mutation following bleomycin injury

Thromb Haemost. 2001 Mar;85(3):441-4.


Increased fibrin deposition following inflammatory lung injury has been proposed to facilitate the development of pulmonary fibrosis. Therefore, factors predisposing to thrombosis may affect the fibrotic response to injury. Activated protein C (aPC) resistance due to the factor V Leiden mutation (FvL) is a common genetic risk factor for vascular thrombosis. To examine the relationship between aPC resistance and the development of pulmonary fibrosis, lung inflammation was induced by bleomycin in mice carrying the FvL mutation. Three weeks following the instillation of 0.0375 U of bleomycin, the lungs of mice homozygous and heterozygous for FvL contained significantly more hydroxyproline (35 +/- 4 and 36 +/- 7 ug hydroxyproline/mg total protein, respectively) than wild-type mice (26 +/- 6 ug/mg protein, p <0.01 for both comparisons). These data demonstrate a strong relationship between aPC resistance and the pulmonary fibrosis that occurs following inflammatory lung injury.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Activated Protein C Resistance / complications
  • Animals
  • Bleomycin
  • Disease Models, Animal
  • Factor V / genetics*
  • Hydroxyproline / metabolism
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Mice
  • Mice, Transgenic
  • Pneumonia / chemically induced
  • Point Mutation
  • Pulmonary Fibrosis / etiology*


  • factor V Leiden
  • Bleomycin
  • Factor V
  • Hydroxyproline