Human OLR1 peptide

Background: Atherosclerosis occurs as a result of a chronic inflammatory response in the arterial wall associated with an increased uptake of low-density lipoprotein by macrophages and the subsequent transformation of this lipoprotein into foam cells. It has been found that miR-188-3p can suppress autophagy and myocardial infarction. Therefore, we conducted the present study with determining the suppressive role played by miR-188-3p in atherosclerosis. Methods: The atherosclerosis model was established using ApoE knockout mice. The healthy C57BL/6J wide-type mice were used as control, while miR-188-3p mimics or inhibitors were applied for the elevation or the depletion of the miR-188-3p expression in mice. The macrophage content was observed in atherosclerotic plaque. Once the miR-188-3p expression was determined, the effects of the over-expression of miR-188-3p on the lipid accumulation and macrophage inflammatory response were accessed. The plasma levels of pro-inflammatory factors and serum RANTES level, as well as OLR1, iNOS, ABCA1 and KLF2 expression were determined in order to evaluate the potential anti-inflammatory and antioxidative activities of miR-188-3p. Results: ApoE knockout mice with atherosclerosis presented with increased lipid accumulation and macrophage content. MiR-188-3p was found to reduce intravascular lipid accumulation in atherosclerotic mice. In addition to the alleviation of macrophage inflammatory response, the upregulation of miR-188-3p also leads to the suppression of oxidation with reduced macrophage accumulation, plasma expression of pro-inflammatory factors and serum RANTES level, OLR1 and iNOS, while it increases ABCA1 and KLF2. Conclusions: In conclusion, the findings from our study found a new potential therapy for atherosclerosis by investigating the inhibitory effects of miR-188-3p on macrophage inflammatory response and oxidation.

Atherosclerosis is a chronic arterial disease and the leading cause of stroke and myocardial infarction. Micro RNAs (miRNAs or miRs) have been reported to act as essential modulators during the progression of atherosclerosis. Although miR-let-7g has been demonstrated to contribute to maintaining endothelial function and vascular homeostasis, it is not known whether miR-let-7g exerts a therapeutic effect on experimental atherosclerosis. The aim of this study was to investigate the effects of miR-let-7g on atherosclerosis in vivo and in vitro and to explore its underlying mechanisms. Data from our study showed that exogenous lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1 or OLR1) overexpression resulted in the significant promotion of proliferation and migration of human aortic smooth muscle cells (ASMCs), whereas such changes induced by LOX-1 were obviously suppressed by transfection of miR-let-7g. We later confirmed that LOX-1 is a potential target of miR-let-7g, and miR-let-7g markedly inhibited LOX-1 expression in ASMCs by directly binding to the 3 untranslated region of LOX-1. Furthermore, in a hyperlipidemic apolipoprotein E knockout (ApoE(-/-)) mouse model, intravenous delivery of miR-let-7g mimics obviously attenuated high-fat diet-induced neointima formation and atherosclerotic lesions, accompanied by the significant downregulation of LOX-1, which was consistent with the effect of miR-let-7g on ASMCs. Taken together, our data revealed that miR-let-7g exhibits anti-atherosclerotic activity, at least partially by targeting the LOX-1 signaling pathway. This study suggests that miR-let-7g may be a therapeutic candidate for treating atherosclerosis, and provides novel insight into miRNA-based therapy for this disease.