Background: Aberrant vascular smooth muscle cell (VSMC) proliferation and migration contribute to the development of vascular pathologies, such as atherosclerosis and postangioplasty restenosis. The aim of this study was to determine whether miR-22-3p plays a role in regulating human artery vascular smooth muscle cell (HASMC) function and neointima formation. Methods: Quantitative real-time PCR (qRT-PCR) and fluorescence in situ hybridization (FISH) were used to detect miR-22-3p expression in human arteries. Cell Counting and EdU assays were performed to assess cell proliferation, and transwell and wound closure assays were performed to assess cell migration. Moreover, luciferase reporter assays were performed to identify the target genes of miR-22-3p. Finally, a rat carotid artery balloon-injury model was used to determine the role of miR-22-3p in neointima formation. Results: MiR-22-3p expression was downregulated in arteriosclerosis obliterans (ASO) arteries compared with normal arteries, as well as in platelet-derived growth factor-BB (PDGF-BB)-stimulated HASMCs compared with control cells. MiR-22-3p overexpression had anti-proliferative and anti-migratory effects and dual-luciferase assay showed that high mobility group box-1 (HMGB1) is a direct target of miR-22-3p in HASMCs. Furthermore, miR-22-3p expression was negatively correlated with HMGB1 expression in ASO tissue specimens. Finally, LV-miR-22-3p-mediated miR-22-3p upregulation significantly suppressed neointimal hyperplasia specifically by reducing HMGB1 expression in vivo. Conclusions: Our results indicate that miR-22-3p is a

Background This study aimed at investigating whether NLRP 3 (the Nod like receptor family, pyrin domain‐containing 3 protein) inflammasome activation induced HMGB 1 (high mobility group box‐1 protein) secretion and foam cell formation in human vascular smooth muscle cells ( VSMC s) and atherosclerosis in ApoE −/− mice. Methods and Results VSMC s or ApoE −/− mice were treated with lipopolysaccharides ( LPS ) and/or ATP or LPS and high‐fat diet to induce NLRP 3 inflammasome activation. HMGB 1 distribution and foam cell formation in VSMC s were characterized. Liver X receptor α and ATP ‐binding cassette transporter expression were determined. The impact of NLRP 3 or receptor for advanced glycation end product silencing, ZYVAD ‐ FMK (caspase‐1 inhibitor), glycyrrhizin ( HMGB 1 inhibitor) or receptor for advanced glycation end product antagonist peptide on HMGB 1 secretion, foam cell formation, liver X receptor α and ATP ‐binding cassette transporter expression was examined. Expression level of HMGB 1 in human atherosclerosis obliterans arterial tissues was characterized. Our results found that NLRP 3 inflammasome activation promoted foam cell formation and HMGB 1 secretion in VSMC s. Extracellular HMGB 1 was a key signal molecule in inflammasome activation‐mediated foam cell formation. Furthermore, inflammasome activation‐induced HMGB 1 activity and foam cell formation were achieved by receptor for advanced glycation end product/liver X receptor α / ATP ‐binding cassette transporter glycyrrhizin. Experiments in vivo found glycyrrhizin significantly attenuated the LPS /high‐fat diet‐induced atherosclerosis and serum HMGB 1 levels in mice. Finally, levels of HMGB 1 and NLRP 3 were increased in tunica media adjacent to intima of atherosclerosis obliteran arteries. Conclusions Our results revealed that HMGB1 is a key downstream signal molecule of NLRP 3 inflammasome activation and plays an important role in VSMC s foam cell formation and atherogenesis by downregulating liver X receptor α and ATP ‐binding cassette transporter expression through receptor for advanced glycation end prod...

Epithelial-mesenchymal transition (EMT) is a key mechanism underlying metastatic breast cancer. Reactive oxygen species (ROS) play an important role in EMT. Heme oxygenase-1 (HMOX-1) can reduce oxidative stress. However, the effect of HMOX-1 on the EMT process in breast cancer cells is unknown. We treated the MCF-7 breast cancer cell line with the HMOX-1 inducer hemin and observed that hemin induced HMOX-1 expression and inhibited migration, invasion and ROS generation in transforming growth factor-β (TGF-β)-treated MCF-7 cells using quantitative RT-qPCR, western blotting, wound-healing and cell invasion assays as well as fluorescent probe DCFDA. Hemin inhibited TGF-β-induced EMT in the MCF-7 cells, whereas HMOX-1 siRNA attenuated the suppressive effect of hemin as determined by the expression and cellular distribution of selected EMT markers. In summary, our results revealed that hemin treatment increased HMOX-1 expression and inhibited TGF-β-induced EMT in MCF-7 cells.

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