Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is one of the major receptors expressed on the endothelium of arterial wall with a key role in endothelial dysfunction and the development of
atherosclerosis. Recent evidence suggested that LOX-1 is upregulated under the condition of
insulin resistance and could be suppressed by the
antidiabetic drugs. We previously also confirmed that
Thiazolidinedione (TZD) has the inhibitory effect on LOX-1 in
ox-LDL-induced endothelial cells. However, the underlying mechanism is unclear. Here we showed that
Rosiglitazone treatment significantly attenuated the expressions of LOX-1,
ICAM-1,
VCAM-1, p47phox, and the atherosclerotic lesions in
ApoE-/- mice with high-fat diet. In vitro, we revealed that
Rosiglitazone inhibited LOX-1 by regulating miR-590-5p.
Ox-LDL-mediated
ICAM-1,
VCAM-1, and p47phox were significantly reduced by
Rosiglitazone, but all reversed after pretreating the cells with antagomiR-590-5p. Induction with
Rosiglitazone activated
PPAR-γ and promoted its nuclear translocation in cultured human umbilical vein endothelial cells (HUVECs). The nuclear
PPAR-γ upregulated the miR-590-5p level through binding to its transcriptional promoter region. Retaining
PPAR-γ in cytoplasm by transfecting with
PPAR-γ⊿NLS plasmid in HUVECs failed to activate miR-590-5p. Mutation of the promoter region of
PPAR-γ also reduced the miR-590-5p promoter
luciferase activity. Collectively, these data indicated that
PPAR-γ may have the therapeutic potential in
atherosclerosis via the transcriptional regulation of miR-590-5p in endothelial cells.