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- Title
Anti-inflammatory properties of high-density lipoproteins in diabetic wound healing.
- Authors
Lotfollahi, Zahra; Williamson, Anna; Primer, Khalia; Dawson, Joe; Psaltis, Peter; Tan, Joanne; Fitridge, Robert; Bursill, Christina
- Abstract
Objectives This study aimed to determine if topical reconstituted high-density lipoproteins (rHDL) have anti-inflammatory effects in diabetic wound healing; explaining their wound healing benefits. We also sought to track the fate of topical rHDL. Methods Diabetes was induced using streptozotocin in C57Bl6/J mice. Two full thickness sub-flank wounds were created, splinted open and rHDL or PBS applied topically daily (n=8-10/group). Inflammatory genes were assessed in wounds collected at baseline, 24h and 3 days post-wounding by qPCR. Wound macrophages were assessed using flow cytometry 7 days post-wounding and area changes measured. Fluorescent rHDL was generated (DiO-rHDL) and its fate was tracked at 15 min, 1, 6, 24h after application by flow cytometry in wounds. Results In diabetic mice, topical rHDL increased the rate of wound closure (23.3%, P<0.05), compared to PBS. rHDL caused early increases in inflammatory genes CCL2 (89%), IL-6 (85%), TGF-β (30%) and NF-κB (31%) after 24h, P<0.05. After 3 days rHDL reversed this and caused a striking drop in CCL2 (155%), IL-6 (92%), TGFβ-1 (48%) and NF-κB (62%), P<0.05 for all. Diabetic wounds had more macrophages than non-diabetic wounds (3.4-fold), P<0.05. Interestingly, diabetic rHDL-treated wounds had less M1 (27%) and M2 (42%) macrophages, compared to diabetic PBS wounds. DiO-rHDL was internalised by wound macrophages within 15 mins. Fibroblasts and endothelial cells internalised DiO-rHDL by 1h. Conclusion Topical rHDL exerts an early inflammatory effect followed by potent anti-inflammatory effects in diabetic wounds. This may explain their wound healing benefits. rHDL is internalised by wound cells and retained.
- Subjects
DIABETES complications; WOUND healing; ANTI-inflammatory agents; INFLAMMATION; CONFERENCES &; conventions; HIGH density lipoproteins; CUTANEOUS therapeutics; PHARMACODYNAMICS
- Publication
Wound Practice & Research, 2021, Vol 29, Issue 2, p113
- ISSN
1837-6304
- Publication type
Article
- DOI
10.33235/wpr.29.2.110-124