Concanavalin A promotes angiogenesis and proliferation in endothelial cells through the Akt/ERK/Cyclin D1 axis

CONTEXT: Concanavalin A (Con A) exhibited multiple roles in cancer cells. However, the role of Con A in endothelial cells was not reported. OBJECTIVE: Our present study investigated the potential angiogenic role of Con A in endothelial cells and ischaemic hind-limb mice. MATERIALS AND METHODS: Human umbilical vein endothelial cells and Ea.hy926 cells were employed to determine the effect of Con A (0.3, 1, and 3 μg/mL) or vehicle on angiogenesis and cell proliferation with tube formation, ELISA, flow cytometry, EdU, and western blot. Hind-limb ischaemic mice were conducted to determine the pro-angiogenic effect of Con A (10 mg/kg) for 7 days. RESULTS: Con A promoted tube formation to about three-fold higher than the control group and increased the secretion of VEGFa, PDGFaa, and bFGF in the medium. The cell viability was promoted to 1.3-fold by Con A 3 μg/mL, and cell cycle progression of G0G1 phase was decreased from 77% in the vehicle group to 70% in Con A 3 μg/mL, G2M was promoted from 15 to 19%, and S-phase was from 7 to 10%. Con A significantly stimulated phosphorylation of Akt and ERK1/2 and expression of cyclin D1 and decreased the expression of p27. These effects of Con A were antagonised by the PI3K inhibitor LY294002 (10 μM) and MEK pathway antagonist PD98059 (10 μM). Moreover, Con A (10 mg/kg) exhibited a repair effect in ischaemic hind-limb mice. DISCUSSION AND CONCLUSIONS: This study will provide a new option for treating ischaemic disease by local injection with Con A.