Vitronectin deficiency is associated with increased wound fibrinolysis and decreased microvascular angiogenesis in mice.
BACKGROUND
Vitronectin has several putative functions including regulating hemostasis, cell adhesion, and cell migration. However, the targeted deletion of vitronectin in mice results in normal development and normal coagulation parameters. To determine whether vitronectin may be necessary for nondevelopmental processes, we examined the response to tissue injury in vitronectin-null mice.


METHODS
We examined wound healing in control and vitronectin-null mice by healing rate, zymography, reverse zymography, and Western blots.


RESULTS
We found that dermal wound healing was slightly delayed in mice lacking vitronectin. More importantly, we found extensive areas of delayed hemorrhage near the sprouting tips of microvessels between days 7 and 14, which temporally coincided with increased urokinase-type plasminogen activator and tissue-type plasminogen activator activity by zymography. Though Western blots confirmed the presence of plasminogen activator inhibitor-1 protein throughout wound repair and reverse zymograms showed decreased plasminogen activator inhibitor-1 activity between days 7 and 14.


CONCLUSIONS
Loss of vitronectin in mice was associated with changes in the fibrinolytic balance, and this may have led to focal sites of delayed hemorrhage. The mechanism that resulted in decreased angiogenesis and the formation of larger blood vessels in response to tissue injury remains unknown. This study suggests that vitronectin may have several distinct functions that are not required for normal development but are manifested in response to tissue injury.
Jang
Y C
YC
Department of Surgery, Puget Sound Health Care System, Seattle, Washington, USA.
Tsou
R
R
Gibran
N S
NS
Isik
F F
FF
D000818:Animals; D005342:Fibrinolysis / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008833:Microcirculation / Q000502:physiology; D018919:Neovascularization, Physiologic; D019096:Vitronectin / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D014945:Wound Healing / Q000502:physiology; D014947:Wounds and Injuries / Q000473:pathology / Q000503:physiopathology*
D019096:Vitronectin