Proliferation of Vascular Smooth Muscle Cells under ox-LDL Is Regulated by Alismatis rhizoma Decoction via InhibitingERK12 and miR-17∼92a Cluster Activation

الملخص EN

Context: Alismatis rhizome decoction (AD) exhibits antiatherosclerotic activities.

The activity of AD against vascular smooth muscle cell (VSMC) proliferation remains unclear.

Objective.

The mechanisms and effects of AD on oxidized low-density lipoprotein (ox-LDL)-induced VSMC proliferation were explored.

Materials and methods.

The male SD rats were fed with AD (2.56 g/mL) or 0.9% NaCl by oral gavage 4 mL twice daily for 7 d.

Then, AD-containing serum (ADcs) 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.

Results.

The ox-LDL-induced miR-17-92a expression promoted VSMC proliferation.

AD and the ERK1/2 inhibitor U0126 (10 μmol/L) inhibited VSMC proliferation and reduced the overexpression of miR-17∼92a.

AD 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 AD 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 α (PPARα) ATP-binding cassette transporter (ABC) A1/G1, which are involved in the process of atherosclerosis.

Conclusions.

AD inhibits ox-LDL-induced VSMC proliferation via inhibiting ERK1/2 and miR-17∼92a activation.

The results provide the multitarget mechanisms for application of AD in the treatment of atherosclerosis.

It would be helpful to the treatment of cardiovascular and cerebral diseases.