Activation of angiogenic gene expression following intradermal delivery of HIF-1α mRNA in rat dermal tissue

Hypoxia-inducible factor-1α (HIF-1α) has emerged as a promising therapeutic strategy for ischemic preconditioning aimed at improving surgical flap viability. In prior work, we established the biologic activity of HIF-1α mRNA in human fibroblasts. In the present study, we evaluated whether delivery of HIF-1α mRNA to rat dermal tissue enhances activation of downstream angiogenic pathways. HIF-1α mRNA encapsulated in lipid nanoparticles was injected intradermally into the dorsal skin of Sprague–Dawley rats. At 24 h post-transfection, HIF-1α expression was found to be significantly elevated compared with controls ( p < 0.05, unpaired Student’s t-test). Moreover, canonical HIF-1α transcriptional targets, including VEGF, ANGPT1, and PGF, demonstrated significant upregulation in treated samples relative to control tissue at 24 h. These data demonstrate effective transfection and downstream pathway activation following HIF-1α mRNA delivery and provide mechanistic support for its use as a therapeutic approach to enhance ischemic flap survival.