The role of microRNA-133b in proliferation of vascular smooth muscle cells induced by endothelial cells under low shear stress / 医用生物力学

ABSTRACT

Objective To investigate the role of microRNAs (miRs) in the proliferation of vascular smooth muscle cells （VSMCs）induced by endothelial insulin-like growth factor-1 (IGF-1) under low shear stress (LowSS). Methods Endothelial cells (ECs) and VSMCs were co-cultured and exposed to normal shear stress (NSS, 1.5 Pa) and LowSS (0.5 Pa) for 12 h with parallel plate flow chamber system, respectively. Real-time PCR was used to examine the expression levels of miRs. The target genes of miR-133b were predicted by multiple algorithms. The expression of polypyrimidine tract binding protein 1 (Ptbp1) and N-myc downstream regulated 1 (Ndrg1) in VSMCs was detected by Western blotting. The VSMC proliferation was detected by EdU flow cytometry assay. Results After treated with recombinant IGF-1, the expression of both miR-133b and miR-378a in VSMCs was increased. Compared with NSS, LowSS significantly induced the expression of miR-133b in the co-cultured VSMCs, but had no obvious effect on miR-378a. In VSMCs, the protein and mRNA levels of Ptbp1 and Ndrg1 were down-regulated by miR-133b mimics. miR-133b inhibitor up-regulated the mRNA levels of Ptbp1 and Ndrg1. miR-133b overexpression promoted the proliferation of VSMCs significantly. Conclusions IGF-1 secreted by ECs in response to LowSS can upregulate the expression of miR-133b in the co-cultured VSMCs, which subsequently depresses the expression of Ptbp1 and Ndrg1, and induces the proliferation of VSMCs eventually. The research findings provide a potential new target for cardiovascular disease therapy.