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.