Effect of fenofibrate on microcirculation and wound healing in healthy and diabetic mice

Abstract

Objective Disturbances in wound healing in patients with hyperglycaemic blood sugar values are a common clinical problem. Recent studies identified PPARα-ligands as potential skin therapeutic agents. The aim of this study was to investigate the effects of oral fenofibrate treatment on dermal wound healing and micro-circulatory parameters in diabetic mice. Methods Dermal wounds were created in CD-1 mice. Mice were randomized into four treatment groups: diabetic mice treated (dbf) or not-treated with fenofibrate (dbnf). As controls served non-diabetic mice treated (ndf) or not-treated with fenofibrate (ndnf). At various points in time microcirculation was analyzed by intravital fluorescent microscopy to determine wound surface area, vessel diameter, plasma leakage, functional capillary density, and leukocyte/endothelium interaction. Results The dbf-mice showed a significantly increased diameter of the venules and the arterioles up to 3 days after wound creation compared to dbnf-mice. However, wound healing was not improved in dbf-compared to dbnf-mice. Surprisingly, all microcirculatory parameter (vessel diameter, plasma leakage and functional capillary density) were not deteriorated in dbnf-compared to ndnf-mice. Conclusion We confirm that high blood sugar values lead to a delayed wound healing, but this could not traced back to altered microcirculatory patterns. Furthermore, in dbf-mice an improved vasodilatatory function of small vessels could be detected, but with no substantial effect on wound healing. Further studies are needed to clarify, if topical application of fenofibrate might be beneficial.

Network proteomic analysis identifies inter-alpha-trypsin inhibitor heavy chain 4 during early human Achilles tendon healing as a prognostic biomarker of good long-term outcomes

“…As an important member of the super-family, it has been reported that the synthesis of PPAR-gamma is increased following exposure to inflammation, and it significantly suppresses collagen production ( 45 ). Relevant to the present discussion, PPAR pathway regulating drugs have been reported to influence wound healing in preclinical models ( 46 ). In addition, PPAR-gamma agonists have also recently been documented to regulate ECM production in human fibroblasts ( 47 ).…”