Low shear stress regulates vascular endothelial cell pyroptosis through miR-181b-5p/STAT-3 axis.

Low shear stress and pyroptosis both play an important role in the onset and development of atherosclerosis (AS). MicroRNAs (miRNAs) are a kind of short (18-22) nucleotide sequences that can bind to the 3'-untranslated region (3'-UTR) of messenger RNA, thereby regulating programmed cell death including pyroptosis. However, the function of miRNAs in cells subjected to shear stress conditions is unknown. Therefore, we conducted the current study to demonstrate the effect of low shear stress on pyroptosis and the underlying mechanism. Human umbilical vein endothelial cells (HUVECs) stimulated by undisturbed shear stress (5 dynes/cm2 ) were the experimental group while HUVECs without shear stress treatment were the control group in our experiments. We observed that shear stress can suppress mechanosensitive miR-181b-5p expression, accompanying the elevated expression of NLRP3 inflammasome-dependent pyroptosis. Introduction of miR-181b-5p could alleviate NLRP3 inflammasome-dependent pyroptosis. Luciferase assay showed specific binding of miR-181b-5p to the 3'-UTR of signal transduction and transcriptional activation factor 3 (STAT-3) gene. Inhibition of STAT-3 gene expression at the posttranscriptional level results in the alleviation of NLRP3 inflammasome-dependent pyroptosis. Besides, the silencing of STAT-3 reduced anti-miR-181b-5p-mediated HUVEC pyroptosis via regulating NLRP3 inflammasome activation. Given the role of mechanosensitive miR-181b-5p and STAT-3 in the shear stress-induced pyroptosis, regulation of their expression levels may be a promising strategy to control AS.

Bioinformatic identification of hub genes and related transcription factors in low shear stress treated endothelial cells.

BACKGROUND: Recent evidences indicated that shear stress is critical in orchestrating gene expression in cardiovascular disease. It is necessary to identify the mechanism of shear stress influencing gene expression in physiology and pathophysiology conditions. This paper aimed to identify candidate hub genes and its transcription factors with bioinformatics. METHODS: We analyzed microarray expression profile of GSE16706 to identify differentially expressed genes (DEGs) in low shear stress (1 dyne/cm2) treated human umbilical vein endothelial cells (HUVECs) compared with static condition for 24 h. RESULTS: 652 DEGs, including 333 up-regulated and 319 down-regulated DEGs, were screen out. Functional enrichment analysis indicated enrichment items mainly included cytokine-cytokine receptor interaction and cell cycle. Five hub genes (CDC20, CCNA2, KIF11, KIF2C and PLK1) and one significant module (score = 17.39) were identified through protein-protein interaction (PPI) analysis. Key transcriptional factor FOXC1 displayed close interaction with all the hub genes via gene-transcriptional factor network. Single-gene GSEA analysis indicated that CDC20 was linked to the G2M_CHECKPOINT pathway and cell cycle pathway. CONCLUSIONS: By using integrated bioinformatic analysis, a new transcriptional factor and hub-genes network related to HUVECs treated with low shear stress were identified. The new regulation mechanism we discovered may be a promising potential therapeutic target for cardiovascular disease.

Identification of key genes in coronary artery disease: an integrative approach based on weighted gene co-expression network analysis and their correlation with immune infiltration.

This study aimed to identify key genes related to coronary artery disease (CAD) and its association with immune cells infiltration. GSE20680 and GSE20681 were downloaded from GEO. We identified red and pink modules in WGCNA analysis and found 104 genes in these two modules. Next, least absolute shrinkage and selection operator (LASSO) logistic regression was used to screen and verify the diagnostic markers of CAD. We identified ASCC2, LRRC18, and SLC25A37 as the key genes in CAD diagnosis. We further studied the immune cells infiltration in CAD patients with CIBERSORT, and the correlation between key genes and infiltrating immune cells was analyzed. We also found immune cells, including macrophages M0, mast cells resting and T cells CD8, were associated with ASCC2, LRRC18 and SLC25A37. Gene enrichment analysis indicated that these genes mainly enriched in apoptotic signaling pathway for biological pathway analysis, riboflavin metabolism for KEGG analysis. The diagnostic efficiency of these key genes measured by AUC in the training set, testing set and validation cohort was 0.92, 0.96 and 0.83, respectively. In conclusion, ASCC2, LRRC18 and SLC25A37 can be used as diagnostic markers of CAD, and immune cell infiltration plays an important role in the onset and development of CAD.

The effect of REDV/TiO2 coating coronary stents on in-stent restenosis and re-endothelialization.

The coronary artery stent has been widely used in clinic. In-stent restenosis was mainly caused by the excessive proliferation of smooth muscle cell and the inflammation due to the metal ion released from stent scaffold of the drug-eluting stent. Thus, to reduce the in-stent restenosis and promote the vascular endothelialization have become a hot research point in this area. In this paper, a nano-TiO2 ceramic coating was deposited on 316L stainless steel to reduce the metal ion release and to inhibit the inflammation reaction. An endothelia cell selective adhesion peptide Arg-Glu-Asp-Val (REDV) coating was prepared on the ceramic coating by a polydopamine technology to promote the endothelialization. The corrosion test indicated that nano-TiO2 ceramic film could effectively decrease the nickel ion released from 316L stainless steel. REDV/TiO2 coating could promote the endothelial cell adhesion and proliferation, meanwhile REDV/TiO2 coating could also increase the nitric oxide concentration. Bare metal stent, TiO2-coated stent and REDV/TiO2-coated stent were implanted in the iliac arteries of rabbit model. In-stent restenosis and re-endothelialization were evaluated at 28 days post-implantation of the stents. The results showed that REDV/TiO2-coated stents could effectively reduce in-stent restenosis and promote re-endothelialization in comparison with TiO2-coated drug-eluting stent and bare metal stent. These results suggest that REDV/TiO2-coated drug-eluting stent maybe a good choice of the application for coronary artery disease.