Atherosclerotic Vascular Smooth Muscle Cells Research Articles

Retracted: Role of miR-181b/Notch1 Axis in circ_TNPO1 Promotion of Proliferation and Migration of Atherosclerotic Vascular Smooth Muscle Cells.

[This retracts the article DOI: 10.1155/2022/4086935.].

Role of miR-181b/Notch1 Axis in circ_TNPO1 Promotion of Proliferation and Migration of Atherosclerotic Vascular Smooth Muscle Cells.

Background The role and expression level change in circ_TNPO1 (hsa_circ_0072951) in atherosclerosis (AS) and VSMC dysfunction remain unknown. In this study, we try to explore the effects of circ_TNPO1 on oxidized low-density lipoprotein (ox-LDL)-induced human vascular smooth muscle cell (VSMC) excessive proliferation and migration, and the potential molecular mechanism. Methods Quantitative real-time polymerase chain reaction (RT-qPCR) and western blot experiment were used to detect the serum samples from AS patients and healthy controls. CCK-8, Transwell, and the dual-luciferase reporter gene assay were used to detect the cell biology. Results In human AS serum and ox-LDL-induced VSMCs, circ_TNPO1 was increased, whereas miR-181b was decreased. Silencing circ_TNPO1 inhibited proliferation and migration activity and reduced protein expression of PCNA, Ki-67, MMP2, and E-cadherin and promoted N-cadherin protein expression in ox-LDL induced VSMCs. Remarkably, miR-181b knockdown or Notch1 overexpression could efficiently offset the proliferation and migration inhibiting effect of circ_TNPO1 knockdown in ox-LDL-induced VSMCs. Furthermore, a molecular mechanism study pointed out that circ_TNPO1 and Notch1 are direct-acting targets of miR-181b. Conclusions In conclusion, our study indicated that circ_TNPO1 promotes the proliferation and migration progression of VSMCs in atherosclerosis through the miR-181b/Notch1 axis.

Effects of Bunao-Fuyuan decoction serum on proliferation and migration of vascular smooth muscle cells in atherosclerotic.

Atherosclerosis (AS) is a chronic inflammatory disease, the main causes of which include abnormal lipid metabolism, endothelial injury, physical and chemical injury, hemodynamic injury, genetic factors and so on. These causes can lead to inflammatory injury of blood vessels and local dysfunction. Bunao-Fuyuan decoction (BNFY) is a traditional Chinese medicine compound that can treat cardiovascular and cerebrovascular diseases, but its effect on AS is still unknown. The aim of this study was to investigate the effect and mechanism of BNFY in proliferation and migration of vascular smooth muscle cells (VSMCs) on AS. At first, the expression of α-SMA protein in ox-LDL-induced VSMCs, which was detected by immunofluorescence staining and western blot. CCK-8 technique and cloning technique were used to detect the cell proliferation of ox-LDL-induced VSMCs after adding BNFY. Meanwhile, the expression of proliferating protein Ki67 was detected by immunofluorescence staining. Western blot was also used to detect the expression of proliferation-related proteins CDK2, CyclinE1 and P27. Flow cytometry was used to detect the effect of BNFY on cell cycle. The effects of BNFY on proliferation and migration of cells were detected by cell scratch test and Transwell. Western blot was used to detect the expression of adhesion factors ICAM1, VCAM1, muc1, VE-cadherin and RHOA/ROCK-related proteins in cells. We found that the expression of AS marker α-SMA protein increased significantly and cells shriveled and a few floated on the medium after induction of ox-LDL on VSCMs. The proliferation rate of ox-LDL VSMCs decreased significantly after adding different doses of BNFY, and BNFY can inhibit cell cycle. Meanwhile, we also found that cell invasion and migration rate were significantly inhibited and related cell adhesion factors ICAM1, VCAM1, muc1 and VE-cadherin were inhibited too by BNFY. Finally, we found that BNFY inhibited the expression of RHOA, ROCK1, ROCK2, p-MLC proteins in the RHOA/ROCK signaling pathway. Therefore, we can summarize that BNFY may inhibit the proliferation and migration of atherosclerotic vascular smooth muscle cells by inhibiting the activity of RHOA/ROCK signaling pathway.

Crystal structure and mutational analysis of the human TRIM7 B30.2 domain provide insights into the molecular basis of its binding to glycogenin-1

Tripartite motif (TRIM)7 is an E3 ubiquitin ligase that was first identified through its interaction with glycogenin-1 (GN1), the autoglucosyltransferase that initiates glycogen biosynthesis. A growing body of evidence indicates that TRIM7 plays an important role in cancer development, viral pathogenesis, and atherosclerosis and, thus, represents a potential therapeutic target. TRIM family proteins share a multidomain architecture with a conserved N-terminal TRIM and a variable C-terminal domain. Human TRIM7 contains the canonical TRIM motif and a B30.2 domain at the C terminus. To contribute to the understanding of the mechanism of action of TRIM7, we solved the X-ray crystal structure of its B30.2 domain (TRIM7B30.2) in two crystal forms at resolutions of 1.6 Å and 1.8 Å. TRIM7B30.2 exhibits the typical B30.2 domain fold, consisting of two antiparallel β-sheets of seven and six strands, arranged as a distorted β-sandwich. Furthermore, two long loops partially cover the concave face of the β-sandwich defined by the β-sheet of six strands, thus forming a positively charged cavity. We used sequence conservation and mutational analyses to provide evidence of a putative binding interface for GN1. These studies showed that Leu423, Ser499, and Cys501 of TRIM7B30.2 and the C-terminal 33 amino acids of GN1 are critical for this binding interaction. Molecular dynamics simulations also revealed that hydrogen bond and hydrophobic interactions play a major role in the stability of a modeled TRIM7B30.2-GN1 C-terminal peptide complex. These data provide useful information that could be used to target this interaction for the development of potential therapeutic agents.

Effect of microRNA-133a-3p/matrix metalloproteinase-9 axis on the growth of atherosclerotic vascular smooth muscle cells.

Atherosclerosis (AS) is the leading cause of cardiovascular disease and poses a threat to human health. MicroRNAs (miRNAs/miRs) are a group of endogenous small non-coding RNAs that have been identified to serve important roles in AS. However, the expression and role of miR-133a-3p in AS remains unclear. The aim of the present study was to investigate miR-133a-3p in AS and to determine its underlying mechanism. The level of miR-133a-3p expression in the blood and vascular plaque tissue of patients with AS was detected via reverse transcription-quantitative PCR (RT-qPCR). The role of miR-133a-3p in human vascular smooth muscle cells (hVSMCs) was investigated, following upregulation and downregulation of this miR in hVSMCs. Cell proliferation and apoptosis were determined using a Cell Counting kit-8 assay and flow cytometry, respectively. The results demonstrated the downregulation of miR-133a-3p in the blood and vascular plaque tissue of patients with AS. Matrix metallopeptidase-9 (MMP-9) was revealed to be a direct target gene of miR-133a-3p, which was upregulated in the blood and vascular plaque tissue of patients with AS. Furthermore, MMP-9 was determined to be negatively regulated by miR-133a-3p in hVSMCs. In addition, significant inhibition of hVSMC proliferation and induction of cell apoptosis were observed following MMP-9 downregulation and following transfection with the miR-133a-3p mimic. The effects of the miR-133a-3p mimic on hVSMC proliferation and apoptosis were reversed by MMP-9 over-expression. Overall, the results indicated that miR-133a-3p was downregulated in AS, which results in the inhibition of hVSMC proliferation and the induction of cell apoptosis via MMP-9. miR-133a-3p may therefore be a promising therapeutic target for the treatment of AS.

Hypernuclear Acetylation in Atherosclerotic Lesions and Activated Vascular Smooth Muscle Cells

Recent studies have implicated acetylation of several nuclear proteins such as histones and p53 on their ϵ-portion of lysine residues in eukaryotic transcription. Here we raised a specific polyclonal antibody against ϵ-acetylated lysine. Using the antibody, we detected hypernuclear acetylation (HNA) in atherosclerotic vascular smooth muscle cells (VSMCs). Thrombin, a humoral factor known to cause activation and proliferation of VSMCs, strongly potentiated HNA in cultured VSMCs. MAP kinase pathway and a signal coactivator CREB binding protein (CBP) were involved in thrombin-induced HNA of VSMCs. Our results suggest that coactivators cooperating with signal-dependent transcription activators play an important role in atherosclerogenesis via HNA in VSMCs.

Long-Term Treatment of Atherosclerotic Minipigs with Isosorbide Dinitrate Restores Nitric Oxide Release from Endothelial Cells, and Inhibits Vascular Smooth Muscle Cell Proliferation

Vascular smooth muscle cells (VSMCs) activation and hyperplasia, the important etiologic factors in atherosclerosis development, are inhibitable by drugs which donate nitric oxide (NO). We tested the hypothesis that administration of ISDN (60 mg/day), a NO donor, would inhibit development of vascular hyperplasia in atherosclerotic minipigs. VSMC proliferation and NO release by endothelial cells (ECs) were investigated in freshly isolated cells from minipigs fed an atherogenic diet with oral ISDN treatment (n = 8) or without (n = 8), or a control diet (n = 8) for 4 months. In ECs, atherosclerosis depressed by 60% NO release and suppressed the L-arginine negative regulatory feedback of the NO-synthase. Concomitantly, a 4-fold increased proliferation (PCNA labelling) and a 2.3-fold activation (PDGF-BB labelling) were observed in atherosclerotic VSMCs. Long-term treatment of atherosclerotic animals with ISDN restored NO release and regulatory processes of NO synthase from ECs, and reduced by half the prolifer...