The role of thrombin-activatable fibrinolysis inhibitor in diabetic wound healing.
BACKGROUND
One of the major complications in patients with diabetes mellitus is impaired wound healing. The fibrinolytic system is involved in parts of the wound healing process and deficiency of thrombin-activatable fibrinolysis inhibitor (TAFI) results in delayed wound closure. Moreover, levels of TAFI are affected by diabetes mellitus. The aim of this study was to elucidate the effect of hyperglycaemia on TAFI and to determine the effect of deficiency of TAFI on wound healing under hyperglycaemic conditions.


METHODS
Hyperglycaemia was induced with streptozotocin (STZ) and used as a model for diabetes mellitus. TAFI plasma levels and TAFI gene expression in the liver were determined. Incisional and excisional wound healing were studied in non-treated and STZ-treated wild-type and TAFI-deficient mice. Wound closure was scored daily as open or closed.


RESULTS
Mice treated with STZ showed hyperglycaemia, and TAFI plasma levels and TAFI gene expression were increased in diabetic mice. TAFI-deficient mice and diabetic wild-type and diabetic TAFI-deficient mice showed delayed wound healing of incisional wounds. No differences were observed between diabetic and non-diabetic TAFI-deficient mice and between diabetic wild-type and diabetic TAFI-deficient mice.


CONCLUSIONS
This study illustrated that TAFI was affected by hyperglycaemia and confirmed that TAFI is involved in wound healing. No additional effect was observed under hyperglycaemic conditions, indicating that deficiency of TAFI did not have an additive or synergistic effect in diabetic wound healing. Further research has to elucidate if TAFI and hyperglycemia affect wound healing via similar mechanisms.
Verkleij
Chantal J N
CJ
Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Roelofs
Joris J T H
JJ
Havik
Stefan R
SR
Meijers
Joost C M
JC
Marx
Pauline F
PF
D000818:Animals; D025901:Carboxypeptidase B2 / Q000097:blood*; D003920:Diabetes Mellitus / Q000097:blood* / Q000473:pathology*; D004195:Disease Models, Animal; D005342:Fibrinolysis; D006943:Hyperglycemia / Q000097:blood / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D014945:Wound Healing
D025901:Carboxypeptidase B2