MiR-21 facilitates the proliferation of smooth muscle cells and atherosclerotic plaque formation by suppressing PTEN to activate AKT

Atherosclerosis (AS) is the major reason for coronary artery disease, cerebral infarction, and peripheral vasculopathy. Lipid metabolic disorder is the pathological basis for AS but but the reasons for this are unclear. MicroRNA (miR)-21 showed differential expression in AS and is related to cell proliferation. This study investigated the expression and effect of miR-21 on AS mice and on the AKT signal pathway. This study utilized LDLr-/- mice to generate an AS model, on which miR-21 expression and its effects on plaque formation were examined. Smooth muscle cells treated with oxLDL were used to investigate the targeted regulation between PTEN and miR-21, along with miR-21' s effects on the AKT signal pathway and cell proliferation. The AS model mice showed significantly higher miR-21 expression (P < 0.05 comparing to control group), accompanied by a lower PTEN expression and an activated AKT signal pathway. The inhibition of miR-21 expression alleviated plaque injury, suggesting the involvement of miR-21 in AS plaque formation. An MTT assay and Western blot found that miR-21 suppressed PTEN expression, activated the AKT signal pathway, and inhibited smooth muscle cell proliferation. A luciferase reporter gene assay confirmed the targeted inhibition of PTEN by miR-21. In summary, MiR-21 facilitates smooth muscle cell proliferation and AS plaque formation possibly by suppressing PTEN and activating AKT. The downregulation of miR-21 might be a novel therapeutic approach for treating AS.