Asymmetric Dimethylarginine Influences p38 Mitogen-Activated Protein Kinase Signaling Pathway on Endothelial Cell Apoptosis Through miR-21

ADMA induces endothelial cell apoptosis through MAPK/P38 signaling and miRNA-21 involves in endothelial cell senescence and apoptosis. Whether ADMA affects endothelial cell apoptosis through miR-21 has not been studied. Therefore, this article investigated ADMA's effect on the apoptosis of endothelial cells. Human umbilical vein endothelial cells (HUVEC) was cultured and treated with PBS and ADMA or ADMA + miR-21 antagonist, respectively, to obtain control group, ADMA group and ADMA + miR-21 antagonist group followed by analysis of miR-21 and p38 mRNA level by qRT-PCR, p-P38, P38, Bcl-2, c-Caspase-3 and Tubulin expression by western blot and cell apoptosis by flow cytometry. Compared to Control group, ADMA group had significantly elevated miR-21 and p-P38 levels (P < 0.01) which were all reduced by miR-21 antagonist (P < 0.05). However, no difference of P38 mRNA level was found among the three groups. Compared with control group, ADMA group showed significantly enhanced cell apoptosis, reduced Bcl-2 level and increased c-Caspase-3 (P < 0.01), which were all significantly reversed in ADMA + miR-21 antagonist group (P < 0.05). ADMA increases miR-21 and p-P38 level, activates P38 MAPK signaling pathway, and promotes endothelial cell apoptosis.