MiR-135a represses oxidative stress and vascular inflammatory events via targeting toll-like receptor 4 in atherogenesis.

Plenty of microRNAs have been identified as critical mediators in atherosclerosis progression, which is still a great threat to human health. Oxidative stress and inflammation have been implicated to contribute a lot to atherosclerosis development. MiR-135a is abnormally expressed in various cancer types, however its function in atherosclerosis is largely unexplored. Ox-LDL is commonly recognized as a crucial atherosclerosis regulator. In our current study, we observed ox-LDL was able to induce RAW264.7 cell apoptosis and meanwhile miR-135a was restrained by ox-LDL both dose-dependently and time- dependently. CD36 has been reported to participate in atherosclerosis process and miR-135a mimics can inhibit its expression while miR-135a inhibitors exhibited a reverse phenomenon. Meanwhile, miR-135a overexpression can suppress foam cell formation, TC, TG levels, and cell apoptosis induced by 20 µg/mL ox-LDL. Subsequently, it was found that miR-135a overexpression can inhibit oxidative stress by decreasing MDA levels, and increasing SOD levels. Reversely, miR-135a inhibition demonstrated an inhibitory effect in vitro. Apart from these, miR-135a can also modulate inflammation molecules including IL-6, IL-1β, and TNF-α. TLR4 was predicted as a target of miR-135a and the negative correlation between them was confirmed by dual-luciferase reporter assay in our study. This work improves our understanding of atherosclerosis events mediated by miR-135a/TLR4 and helps to develop new approaches for atherosclerosis.

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