Abstract
Objectives:
Thrombotic complications in multiple myeloma (MM) impairs the quality of life of patients. Metformin has a certain effect on anti-thrombosis, but its role and mechanism in MM-induced thrombosis are still uncovered. Therefore, this study evaluated the effect of metformin on MM-induced thrombosis.
Methods:
Human umbilical vein endothelial cells (HUVECs) were exposed to normal serum (15%), MM serum (15%), metformin (0.01 mmol/L), or MM serum and metformin simultaneously. The expression of tissue factor (TF) in HUVECs was detected by flow cytometry and quantitative real-time PCR (qRT-PCR). QRT-PCR was also used to determine the expressions of endothelial protein C receptor (EPCR) and miR-532. The generation of thrombin and activated protein C was measured by thrombin generation and protein C activation assays. And EPCR, extracellular signal-regulated kinase (ERK) 1/2, p38 mitogen activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathway related protein expressions were detected by western blot.
Result:
MM serum increased the expressions of TF, EPCR and miR-532, and induced thrombin generation and protein C activation in HUVECs. Based on the MM serum treatment, metformin decreased these expressions and inhibited the thrombin generation and protein C activation in HUVECs. However, miR-532 mimic reversed the effect of metformin and promoted the levels of thrombosis related indicators in HUVECs. Moreover, metformin activated the EPCR, ERK 1/2, p38 MAPK and NF-κB pathways but miR-532 mimic suppressed the activation of pathways.
Conclusion:
Metformin played an inhibitory effect on MM serum-induced HUVEC thrombosis, suggesting that metformin could serve as a novel antithrombotic approach for MM patients.
Full text
