microRNA-301a-3p is a potential biomarker in venous ulcers vein and gets involved in endothelial cell dysfunction

Venous ulcer is a common contributor to chronic venous insufficiency (CVI) of lower limbs, which seriously affects the life quality of patients. In this study, we researched the expression characteristics of microRNA-301a-3p (miR-301a-3p) in patients with CVI and investigated the impact of miR-301a-3p on the dysfunction of human umbilical vein endothelial cells (HUVECs). The plasma level of miR-301a-3p in normal controls, patients with varicose great saphenous vein, and patients with the venous ulcer of lower limbs were measured. We adopted Interleukin-1 beta (IL-1 beta), H2O2, and oxygen and glucose deprivation (OGD) to induce endothelial cell injury in vitro. In this way, we evaluated the influence of miR-301a-3p on HUVEC viability, apoptosis, inflammatory response, and oxidative stress. Our data showed that miR-301a-3p was substantially overexpressed in patients with lower limb venous ulcers. The viability of HUVECs decreased, and miR-301a-3p was up-regulated after IL-1 beta, H2O2, and OGD treatment. miR-301a-3p inhibition greatly ameliorated the dysfunction and cell damage of HUVECs, promoted IGF1/PI3K/Akt/PPAR gamma, and down-regulated NF-kappa B/MMPs. The phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002) or the peroxisome proliferator-activated receptor-gamma (PPAR gamma) inhibitor (GW9661) reversed the anti-inflammatory, antioxidant, and anti-apoptotic effects mediated by miR-301a-3p down-regulation. The nuclear factor-kappa B (NF-kappa B) inhibitor lessened cell injury mediated by miR-301a-3p overexpression. In terms of the mechanism, miR-301a-3p targeted the 3MODIFIER LETTER PRIMEUTR of Insulin-like growth factor-1 (IGF1) and repressed the profile of IGF1. Thus, miR-301a-3p mediates venous endothelial cell damage by targeting IGF1 and regulating the IGF1/PI3K/Akt/PPAR gamma/NF-kappa B/MMPs pathway.