Gene Therapy for Fibroproliferative Phase Ards

  • Paul N. Reynolds
  • Mitchell A. Olman


Following an acute injury to the lung, restoration of the normal alveolar architecture and function is the ideal outcome. Unfortunately, following a myriad of endovascular or inhaled toxins, a series of temporally and spatially overlapping injury and repair events all too often result in a dysfunctional fibrotic lung. The fibroproliferative phase of acute lung injury is characterized by progressive accumulation of interstitial and alveolar myofibroblasts and matrix leading to impaired gas exchange and severely reduced lung compliance. The critical feature of this late stage (1–4 weeks after injury) of the injury/repair continuum is the disruption of normal alveolar architecture. For normal lung function to return, both the liquid and protein barrier function and the diffusion properties of the alveolar-capillary structures must be restored. The requisite temporal and spatial coordination of alveolar proteolysis, cell proliferation, apoptosis, angiogenesis, matrix synthesis and epithelial cell re-population provide ample and complementary biological pathways for targeting gene therapy (1, 2, 3, 4, 5, 6). This chapter will review the alveolar architectural and biochemical abnormalities that occur within the first few weeks of a severe lung injury and discuss potential targets, successes and delivery modes for gene therapy designed to reduce the fibroproliferative response.


Cystic Fibrosis Gene Therapy Lung Injury Plasminogen Activator Acute Lung Injury 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Paul N. Reynolds
    • 1
  • Mitchell A. Olman
    • 1
  1. 1.University of Alabama at BirminghamBirminghamUSA

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