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.
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).
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.