title: Hyperglycemia Interacts with Ischemia in a Synergistic Way on Wound Repair and Myofibroblast Differentiation.
abstract: BACKGROUND
  Hyperglycemia is known to adversely affect the outcome of ischemic insults, but its interaction with ischemia has not been investigated in wound repair yet. In this study, we develop a new animal model allowing to investigate the interaction between hyperglycemia and ischemia during the wound repair process. We focus on myofibroblast differentiation, a key element of wound repair.
  
  
  METHODS
  Ischemia was inflicted in Wistar rats by resection of the femoral to popliteal arteries on the left side, whereas arteries were dissected without resection on the right side. Full-thickness skin wounds (1 cm(2)) were created on both feet. Hyperglycemia was induced by injection of streptozotocin. Normoglycemic animals served as control (n = 23/group). Blood flow, wound closure, and myofibroblast expression were measured.
  
  
  RESULTS
  Wound closure was significantly delayed in ischemic compared with nonischemic wounds in all rats. This delay was almost 5-fold exacerbated in hyperglycemic rats compared with normoglycemic rats, while hyperglycemia alone showed only a slight effect on wound repair. Delayed wound repair was associated with impaired wound contraction and myofibroblast differentiation.
  
  
  CONCLUSIONS
  Our model allows to specifically quantify the effect of hyperglycemia and ischemia alone or in combination on wound repair. We show that hyperglycemia amplifies the inhibitory effect of ischemia on wound repair and myofibroblast expression. Our data reveal for the first time the synergic aspect of this interaction and therefore stress the importance of a strict glycemic control in the management of ischemic wounds.
authors: Division of Plastic, Reconstructive and Aesthetic Surgery, Geneva University Hospitals, Geneva, Switzerland; Faculty of Medicine, University of Geneva, Geneva, Switzerland; and Laboratory of Tissue Repair and Regeneration, Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.
authors: Mickaël
authors: M
authors: Tobalem
authors: Division of Plastic, Reconstructive and Aesthetic Surgery, Geneva University Hospitals, Geneva, Switzerland; Faculty of Medicine, University of Geneva, Geneva, Switzerland; and Laboratory of Tissue Repair and Regeneration, Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.
authors: Dominik
authors: D
authors: Lévigne
authors: Division of Plastic, Reconstructive and Aesthetic Surgery, Geneva University Hospitals, Geneva, Switzerland; Faculty of Medicine, University of Geneva, Geneva, Switzerland; and Laboratory of Tissue Repair and Regeneration, Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.
authors: Ali
authors: A
authors: Modarressi
authors: Division of Plastic, Reconstructive and Aesthetic Surgery, Geneva University Hospitals, Geneva, Switzerland; Faculty of Medicine, University of Geneva, Geneva, Switzerland; and Laboratory of Tissue Repair and Regeneration, Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.
authors: Fatemeh
authors: F
authors: Atashi
authors: Division of Plastic, Reconstructive and Aesthetic Surgery, Geneva University Hospitals, Geneva, Switzerland; Faculty of Medicine, University of Geneva, Geneva, Switzerland; and Laboratory of Tissue Repair and Regeneration, Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.
authors: Frederic
authors: F
authors: Villard
authors: Division of Plastic, Reconstructive and Aesthetic Surgery, Geneva University Hospitals, Geneva, Switzerland; Faculty of Medicine, University of Geneva, Geneva, Switzerland; and Laboratory of Tissue Repair and Regeneration, Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.
authors: Boris
authors: B
authors: Hinz
authors: Division of Plastic, Reconstructive and Aesthetic Surgery, Geneva University Hospitals, Geneva, Switzerland; Faculty of Medicine, University of Geneva, Geneva, Switzerland; and Laboratory of Tissue Repair and Regeneration, Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.
authors: Brigitte
authors: B
authors: Pittet-Cuénod