Oleic acid induces A7r5 cell proliferation and migration associated with increased expression of HGF and p-p38

The phenotypes and mechanisms underlying the proliferation and migration of vascular smooth muscle cells (VSMCs) induced by oleic acid (OA) are not completely understood. Therefore, the aim of the present study was to further elucidate the effects of OA on the proliferation and migration of VSMCs. Using A7r5 cells, the hepatocyte growth factor (HGF) inhibitor PHA665752 and the p38 MAPK inhibitor SB203580 were utilized, and Cell Counting Kit-8 (CCK-8) assays, Transwell assays, flow cytometry, ELISAs, western blotting and reverse transcription-quantitative PCR (RT-qPCR) were conducted to assess the effects of OA. CCK-8 assays indicated that OA promoted (at 5 and 50 µmol/l) or inhibited (at 800 µmol/l) A7r5 cell proliferation in a time- and concentration-dependent manner (P<0.05). Transwell assays revealed that OA also promoted (at 50 µmol/l) or inhibited (at 800 µmol/l) A7r5 cell migration (P<0.05). Moreover, cell-cycle analysis identified that 50 µmol/l OA reduced the cellular population in the G(0)/G(1) phase and enhanced the cellular population in the S phase (P<0.05), whereas 800 µmol/l OA increased the cell number in the G(0)/G(1) phase and decreased the cell number in the S phase (P<0.05). In addition, OA promoted (at 50 µmol/l) or inhibited (at 800 µmol/l) the expression level of HGF in A7r5 cells, as demonstrated via ELISA, western blotting and RT-qPCR analyses (P<0.05). It was also found that OA promoted (at 50 µmol/l) or inhibited (at 800 µmol/l) the expression level of phosphorylated (p)-p38 in A7r5 cells, as indicated by western blotting (P<0.05). Furthermore, the cell proliferation, migration and HGF expression induced by OA (50 µmol/l) were mitigated by treatment with PHA665752 (0.1 µmol/l) (P<0.05), and the cell proliferation, migration and p-p38 expression induced by OA (50 µmol/l) were mitigated by SB203580 (2 µmol/l) (P<0.05). Thus, the results suggested that OA served a role in the proliferation and migration of VSMCs via HGF and the p38 MAPK pathway. Moreover, the proliferation and migration of VSMCs induced by OA was associated with increased expression levels of HGF and p-p38. Taken together, OA, HGF and p38 MAPK may be potential therapeutic targets for the treatment of atherosclerosis.