| Summary: | 博士 === 臺北醫學大學 === 醫學科學研究所 === 101 === Ursolic acid (UA), a triterpenoid compound found in plants, is used in the human diet and in medicinal herbs and possesses a wide range of biological benefits including antioxidative, anti-inflammatory, and anticarcinogenic effects. However, until now, there are rare evidences to promote the benefit of UA on neovascularization and anti-atherogenesis. Therefore, we performed the studies using human coronary artery endothelial cells (HCAECs) in vitro and C57BL/B6 mice in vivo to identify the effects of UA in these issues. Furthermore, we explored the probably underlying mechanisms in this study. The results demonstrated that UA enhances collateral blood flow recovery and capillary density through induction of neovascularization in hind limb ischemia C57BL/B6 mice. In in vitro data showed that UA increases tube formation and migration capacities in human endothelial cells, and exposing HCAECs to UA increased allograft inflammatory factor-1(AIF-1) expression through a nitric oxide-related mechanism. Additionally, high-mobility group box 1 (HMGB1) is known to mediate vascular inflammation. We have demonstrated that HMGB1 enhances oxidized low density lipoprotein (oxLDL) uptake through induction of lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) in HCAECs and C57BL/B6 mice in this study. Exposing HMGB1-stimulated HCAECs and hypercholesterolemic C57BL/B6 mice to UA decreased the LOX-1-mediated absorption of oxLDL through a cyclooxygenase (COX)-2-related NO signaling pathway. These findings suggest that UA may be a potential therapeutic agent in the hypercholesterolemia-induced atherosclerosis and induction of neovascularization. It provides a novel mechanistic insight into the potential effects of UA on ischemic vascular diseases and atherosclerosis.
|
|---|
