Evidence-Based Practice
The ten studies included samples from 84 individuals with DFUs, 15 with CVLUs, and 52 with acute wounds. In-vitro analysis found that overexpression of miR-503, miR-181-5p, miR-23a-3p, miR-144-3p, miR-195-5p, miR-205-5p, and miR-301a-3p led to endothelial dysfunction, impairing endothelial tube formation and angiogenesis. Conversely, upregulation of miR-21-5p, miR-204-3p, and miR-27b improved vascular function and endothelial tube formation. MiR-195-5p, miR-205-5p targeted VEGF-A, while MiR-27b targeted VEGF-A, Nrf2 and SDF-1ɑ signaling pathway. MiR-301a-3p and miR-503 targeted IGF-1, miR-23a-3p targets SDF-1ɑ, and miR-181-5p targeted Nrf2/3’UTR. Additionally, miR-144-3p targeted NFE2L2/ HIF1 signaling pathway. Overexpression of miR-181-5p increased senescence in endothelial cells. A wound dressing coated with anti-miR-92a improved angiogenesis by targeting endothelial-specific transcripts in-vitro and in-vivo. Six in-vivo studies with animal models corroborated with the in-vitro findings.
Impaired angiogenesis is a hallmark of DFUs/VLUs and can be more evident with aging. Age-related oxidative stress leads to the accumulation of senescent cells, causing endothelial cell dysfunction and delayed wound healing. Senescent cells can also become dysregulated in a hyperglycemic environment, affecting endothelial tube formation and, consequently, angiogenesis. MiRNAs are important mediators involved in regulation of angiogenesis, cell migration, and consequently wound healing. Identifying the specific microRNAs and their target pathways provides valuable insights, guiding future research toward potential therapeutic targets for the treatment of diabetic and venous leg ulcers.