Proliferation of Vascular Smooth Muscle Cells under ox-LDL Is Regulated by Decoction via InhibitingERK1/2 and miR-17∼92a Cluster Activation.

: decoction () exhibits antiatherosclerotic activities. The activity of against vascular smooth muscle cell (VSMC) proliferation remains unclear. . The mechanisms and effects of on oxidized low-density lipoprotein (ox-LDL)-induced VSMC proliferation were explored. . The male SD rats were fed with (2.56 g/mL) or 0.9% NaCl by oral gavage 4 mL twice daily for 7 d. Then, -containing serum (cs) was collected. MTS assay was applied to measure the VSMC viability. The proliferation of VSMCs was detected by 5-bromodeoxyuridine (BrdU) immunocytochemistry. The microRNA (miRNA) profiling was performed, and the target genes of miRNAs were searched from the TargetScan 7.2 database. The expressions of matrix metalloproteinases-2/9 (MMP-2/9), cyclin D1/E, cyclin-dependent kinase inhibitor 1B (p27), extracellular regulated protein kinases 1/2 (ERK1/2), and ERK1/2 phosphorylation were examined by western blotting or quantitative reverse transcription PCR. . The ox-LDL-induced miR-17-92a expression promoted VSMC proliferation. and the ERK1/2 inhibitor U0126 (10 mol/L) inhibited VSMC proliferation and reduced the overexpression of miR-17∼92a. was found to inhibit phosphorylation of ERK1/2 and reduced the expression of MMP-2/9 in VSMCs. The expression of cyclin D1/E was suppressed, and p27 was elevated following treatment with as well as ERK1/2 inhibitor. According to the TargetScan 7.2 database, the target genes of miR-17∼92a act on tissue inhibitors of metalloproteinases (TIMPs)-MMPs, p27/21 cyclins, and peroxisome-proliferator-activated receptor (PPAR) ATP-binding cassette transporter (ABC) A1/G1, which are involved in the process of atherosclerosis. . inhibits ox-LDL-induced VSMC proliferation via inhibiting ERK1/2 and miR-17∼92a activation. The results provide the multitarget mechanisms for application of in the treatment of atherosclerosis. It would be helpful to the treatment of cardiovascular and cerebral diseases.