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Atherosclerosis (AS) is the most dangerous factor for human death, which is a lipid‐driven chronic inflammatory disorder of the arteries. Growing evidence has showed that microRNAs play an important role in AS. However, the role of mir‐193b‐3p in atherosclerosis has been poorly studied to date. Therefore, we focused on the potential role of miR‐193b‐3p in atherosclerosis. The expressions of miR‐193b‐3p in the serum of AS patients were detected. We also established an oxidized low density lipoprotein (ox‐LDL)‐induced human umbilical vein endothelial cells (HUVECs) apoptosis model in vitro. The mRNA and protein levels of target molecules were detected by RT‐qPCR and Western blotting. Apoptosis of HUVECs was determined by Annexin V/PI staining on a flow cytometry. The potential molecular targets of miR‐193b‐3p were investigated by applying such technologies as dual‐luciferase reporter and RIP assay. Our study showed that miR‐193b‐3p expression level was significantly lower in AS patients than controls. ROC curve analysis showed that the areas under the curve (AUC) of plasma miR‐193b‐3p was 0.859. We also found that miR‐193b‐3p was decreased in ox‐LDL‐induced HUVECs and knockdown of miR‐193b‐3p suppressed ox‐LDL‐induced HUVECs injury. By using bioinformatics analysis, aldehyde dehydrogenase (ALDH2) was predicted as a downstream target of miR‐193b‐3p. The ALDH2 gene is also involved in the development of atherosclerosis. Meanwhile, inhibition of miR‐193b‐3p and ALDH2 protects ox‐LDL‐induced HUVECs against endoplasmic‐reticulum (ER) stress. In conclusion, inhibition of miR‐193b‐3p was able to suppress ox‐LDL‐induced injury in AS through targeting ALDH2 and reducing ER stress. [ABSTRACT FROM AUTHOR]

Pyroptosis is a form of cell death that is uniquely dependent on caspase‐1. Pyroptosis involved in oxidized low‐density lipoprotein (ox‐LDL)‐induced human macrophage death through the promotion of caspase‐1 activation is important for the formation of unstable plaques in atherosclerosis. The mitochondrial outer membrane protein NIX directly interacts with microtubule‐associated protein 1 light chain 3 (LC3). Although we previously showed that NIX‐mediated mitochondrial autophagy is involved in the clearance of damaged mitochondria, how NIX contributes to ox‐LDL‐induced macrophage pyroptosis remains unknown. Here, immunoperoxidase staining Nix expression decreased in human atherosclerosis. When we silenced NIX expression in murine macrophage cell, active caspase‐1, and mature interleukin‐1β expression levels were increased and LC3 was reduced. In addition, LDH release and acridine orange and ethidium bromide staining indicated that damage to macrophage cell membranes induced by ox‐LDL was substantially worse. Moreover, intracellular reactive oxygen species and NLRP3 inflammasome levels increased. Taken together, these results demonstrated that NIX inhibits ox‐LDL‐induced macrophage pyroptosis via autophagy in atherosclerosis. [ABSTRACT FROM AUTHOR]

Atherosclerosis (AS) is one of the most common chronic inflammatory diseases and a major cause of morbidity and mortality. However, the underlying molecular mechanisms of the progression of AS are still largely unknown. Increasing evidence has demonstrated that long noncoding RNAs (lncRNAs) play important roles in a variety of biological processes and the physiological and pathological progression of human diseases. In this study, we aimed to explore the role and underlying molecular mechanism of lncRNA MEG3 in Raw264.7 cells treated with oxidized low‐density lipoprotein (ox‐LDL). First, we found that ox‐LDL inhibited the cell viability and proliferation, increased TNFα and IL1β secretion and induced the apoptosis of Raw264.7 cells. Second, we demonstrated that ox‐LDL upregulated MEG3 expression and that knockdown of MEG3 inhibited the action of ox‐LDL in Raw264.7 cells. Third, we showed that MEG3 sponged miR‐204 in Raw264.7 cells treated with ox‐LDL. Fourth, we demonstrated that miR‐204 regulated the expression of cyclin‐dependent kinase inhibitor 2A (CDKN2A) in Raw264.7 cells treated with ox‐LDL. Finally, we revealed that MEG3 exerted its function via the regulation of the MEG3/miR‐204/CDKN2A regulatory axis in Raw264.7 cells treated with ox‐LDL. In summary, our study identified the role of the MEG3/miR‐204/CDKN2A pathway in Raw264.7 cells treated with ox‐LDL, revealed a novel regulatory pathway in AS and indicated potential novel characteristic biomarkers and therapeutic targets for AS. [ABSTRACT FROM AUTHOR]

Macrophages and oxidized low-density lipoprotein (ox-LDL) have been verified playing vital roles in the pathogenesis of atherosclerosis (AS). Previous studies demonstrated that microRNA-29a (miR-29a) was upregulated in many atherogenic process and cells, thus acting as an important participant in AS. But the detailed regulation mechanism of miR-29a in AS has not been fully understood. In our study, we demonstrated a positive feedback loop of ox-LDL-SRA-miR-29a. Furthermore, we found that YY1 and STAT1 were upregulated in ox-LDL-stimulating macrophages followed by translocation in the nucleus and binding to the transcriptional promoter region of miR-29a, thus leading to the increase of miR-29a expression. In addition, we demonstrated that JAK1/2 signaling was involved in miR-29a upregulation. Finally, we found that miR-29a played important roles in the secretion of proinflammation factors and lipid uptake in macrophages. We uncovered the molecular mechanism and provide novel insights into the function and regulatory network of miR-29a expression regulated by ox-LDL in macrophages. [ABSTRACT FROM AUTHOR]

The mechanism of the regulatory roles of stromal cell derived factor-1 (SDF-1)/C-X-C motif receptor 4 (CXCR4) on cell proliferation and apoptosis in vascular smooth muscle cells (VSMCs) via the protein kinase C (PKC) and nuclear factor-kappa B (NF-κB) signalling pathways have been investigated. Rat aortic VSMCs were treated with control or an oxidised low-density lipoprotein (ox-LDL) atherosclerosis (AS) model. Cells exposed to the AS model were treated with SDF-1 plus inhibitors specific for PKC (Ro31-8220), CXCR4 (12G5) or NF-κB (pyrrolidine dithiocarbamate, PDTC). Cell proliferation was measured with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and apoptosis by flow cytometry. NF-κB protein expression was analysed using Western blotting. The proliferation rate in the AS model group was significantly higher than the control group, but lower than the SDF-1 group ( P < 0.05). Apoptosis in the AS model group (ox-LDL) was significantly higher than the normal control group ( P < 0.05). In addition, the apoptosis rate in the SDF-1 group was significantly lower than the normal control group ( P < 0.05); however, there was no difference from the Ro31-8220 group. NF-κB protein expression in the SDF-1 group was significantly higher than the AS model (ox-LDL) group ( P < 0.05). In conclusion, SDF-1 can promote the proliferation of VSMCs induced by ox-LDL and inhibit cell apoptosis, via the SDF-1/CXCR4 axis. [ABSTRACT FROM AUTHOR]