Glycation of Apolipoprotein A-IV Impairs Angiogenesis Through The Orphan Nuclear Receptor Nur77

Abstract

Background Apo A-Ⅳ played an key role in Cardiovascular diseases, but the effect and mechanism of glycated apo A-Ⅳ on angiogenesis remains unclear. Methods In this study, we demonstrated that oral administration of glycated apoA-Ⅳ impaired blood perfusion recovery in a mouse hind-limb ischemia model. A reduction in blood perfusion recovery at day 21 was observed in the ischemic tissue of apoA-Ⅳ and glycated apoA-Ⅳ-treated mice. Results In this study, we demonstrated that glycated apo A-Ⅳ impaired blood perfusion recovery in a mouse hind-limb ischemia model. And in vitro study also showed that glycated apo A-Ⅳ inhibited the migration, proliferation, and tube-formation abilities of endothelial cells. Further research revealed that glycated apo A-Ⅳ regulated angiogenesis partly by interrupting Nur77. In addition, CML levels were increased in patients with Lower limb circulation (n = 30) compared with those with no limb circulation(n = 50). Conclusions We found impaired angiogenesis induced by glycated apo A-Ⅳ might contribute to poor coronary collateral growth by inhibit the expression of Nur77.