The biological function of the intronic microRNA-28 (miR-28) may be associated with the biological roles of its host gene, LIM domain lipoma-preferred partner (LPP). LPP has been reported to promote smooth muscle cell migration in arterial injury and atherosclerosis. However, the mechanism of miR-28 in atherosclerosis remains unclear. In the current study, the aim was to validate the inhibitory effect of miR-28-5p on extracellular signal-regulated kinase 2 (ERK2), to investigate its biological role in atherosclerosis and its association with cardiovascular disease. Western blotting and stem-loop reverse transcription-quantitative polymerase chain reaction combined with TaqMAN microRNA analysis was conducted. The current study demonstrated that miR-28-5p upregulated the expression of ATP-binding cassette transporter A1 (ABCA1) via the inhibition of ERK2 in HepG2 cells. In addition, increased levels of plasma miR-28-5p were positively correlated with the levels of high-density lipoprotein cholesterol in patients with unstable angina. This suggests that miR-28-5p participates in atherosclerosis via ERK2-mediated upregulation of the ABCA1 pathway. [ABSTRACT FROM AUTHOR]