Abstract
High serum beta 2 glycoprotein I (β2GPI) is associated with complications of type 2 diabetes mellitus (DM), and especially microvascular disorders. In contrast, reduced β2GPI (Rβ2GPI) can prevent diabetic vascular injury. This study aimed to investigate the protective function of Rβ2GPI in DM vascular disorders, and to assess the under lying mechanisms. High glucose-induced injury in human umbilical vein endothelial cells (HUVECs) was used to model hyperglycemia. Alow concentration of Rβ2GPI (0.5 μM), but not β2GPI, mitigated high glucose-induced cell injury. High glucose decreased miR-21 expression and Akt phosphorylation at 6 h, but facilitated their expression at 48 h. Moreover, high glucose decreased phosphatase and tensin homolog deleted on chromosome ten(PTEN) expression at 6 h, but facilitatedits expression at 48 h. Importantly, by promoting miR-21 expression, Rβ2GPI mitigated high glucose-induced PTEN expression, reduced Akt phosphorylation and nitric oxide synthase activity, and increased cyclooxygenase-2 activity and cell loss. Similar to Rβ2GPI, an miR-21 mimic (1 pM) and PTEN inhibition (1 μM bpV, or PTEN silencing) exerted protective action, while an Akt signaling pathway inhibitor (LY294002, 1 μM) aborted the effect of Rβ2GPI on high glucose-induced cell injury. Finally, Rβ2GPI inhibited high glucose-induced apoptosis via a mitochondria-dependent pathway. These data reveal that Rβ2GPI exerts protective action in high glucose-induced HUVEC injury. The mechanism is related to the miR-21-PTEN-Akt pathway and mitochondria-dependent apoptosis. This study provides in vitro data supporting the therapeutic effect of Rβ2GPI in diabetic vascular injury.