Using experimental data mining approaches combined with experiments, we found that, among 109 miRNAs, miR-155, and miR-221 are significantly modulated in all four hyperlipidemia-related diseases (HRDs), namely atherosclerosis, NAFLD, obesity and type II diabetes (T2DM).
These results suggest that GAS5 can trigger inflammatory response and MMP expression by acting as a sponge of miR-221, which may facilitate fibrous cap degradation and aggravate atherosclerotic plaque destabilization, supporting a promising therapeutic agent against atherosclerosis.
By controlling the expression levels of their targets, several miRNAs have been shown to modulate the function of endothelial cells (miR-221/222 and -126), vascular smooth muscle cells (miR-143/145) and macrophages (miR-33, -758, and -26), thereby regulating the development and progression of atherosclerosis.
These findings suggest that manipulation of the miR-221/222-Ets-1-p21 pathway may offer a novel strategy for treatment of endothelial apoptosis and atherosclerosis.
Stroke patients and atherosclerosis subjects had significantly higher miR-21 and lower miR-221 serum levels than healthy controls, while the miR-145 expression was too low to provide useful information in this regard.
The opposite cellular effects of miR-221/222 on VSMCs and ECs may have important therapeutic applications in many vascular diseases such as atherosclerosis and restenosis after angioplasty.