Impaired wound healing and angiogenesis in eNOS-deficient mice

Paul C. Lee*, A. Neil Salyapongse, Gwynne A. Bragdon, Larry L. Shears, Simon C. Watkins, Howard D.J. Edington, Timothy R. Billiar

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

354 Scopus citations


A role for nitric oxide (NO) in wound healing has been proposed; however, the absolute requirement of NO for wound healing in vivo and the contribution of endothelial NO synthase (eNOS) have not been determined. Experiments were carried out using eNOS gene knockout (KO) mice to determine the requirement for eNOS on wound closure and wound strength. Excisional wound closure was significantly delayed in the eNOS KO mice (29.4 ± 2.2 days) compared with wild-type (WT) controls (20.2 ± 0.4 days). At 10 days, incisional wound tensile strength demonstrated a 38% reduction in the eNOS KO mice. Because effective wound repair requires growth factor-stimulated angiogenesis, in vitro and in vivo angiogenesis assays were performed in the mice to assess the effects of eNOS deficiency on angiogenesis. Endothelial cell sprouting assays confirmed in vitro that eNOS is required for proper endothelial cell migration, proliferation, and differentiation. Aortic segments harvested from eNOS KO mice cultured with Matrigel demonstrated a significant reduction in endothelial cell sprouting and [3H]thymidine incorporation compared with WT mice at 5 days. Capillary ingrowth into subcutaneously implanted Matrigel plugs was significantly reduced in eNOS KO mice (2.67 ± 0.33 vessels/plug) compared with WT mice (10.17 ± 0.79 vessels/plug). These results clearly show that eNOS plays a significant role in facilitating wound repair and growth factor-stimulated angiogenesis.

Original languageEnglish
Pages (from-to)H1600-H1608
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number4 46-4
StatePublished - Oct 1999
Externally publishedYes


  • Endothelial cell
  • Endothelial nitric oxide synthase
  • Endothelial nitric oxide synthase knockout
  • Nitric oxide
  • Nitric oxide synthase
  • Wound repair


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