BAF60a Deficiency in Vascular Smooth Muscle Cells Prevents Abdominal Aortic Aneurysm by Reducing Inflammation and Extracellular Matrix Degradation

Chang, Ziyi; Zhao, Guizhen; Zhao, Yang; Lu, Haocheng; Xiong, Wenhao; Liang, Wenying; Sun, Jin; Wang, Huilun; Zhu, Tianqing; Rom, Oren; Guo, Yanhong; Fan, Yanbo; Chang, Lin; Yang, Bo; Garcia-Barrio, Minerva T.; Lin, Jiandie D.; Chen, Y. Eugene; Zhang, Jifeng

doi:10.1161/atvbaha.120.314955

Cited by 35 publications

(28 citation statements)

References 54 publications

(58 reference statements)

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“…On the other hand, macrophages and others can secrete a variety of proteolytic enzymes to further degrade elastin and collagen in the vascular wall, resulting in decreased compliance and elasticity of the vascular wall. Inflammatory factors play an important role in the occurrence and development of AAA [ 31 ]. Currently, there are few studies on the role of the vasostatin-1 gene in aortic aneurysm.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Protective effect of vasostatin-1 plasmid-like nanoparticles on aortic aneurysm and its mechanism

Wang

Peng

et al. 2021

Bioengineered

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Vasostatin 1 (VS-1) plays an important role in the regulation of various tissue injury and repair processes, but its role in aortic aneurysm remains unclear. The plasmid-like nanoparticles containing the vasostatin-1 gene Pul-PGEA-pCas-sgVs-1 were constructed, and their guarantee, safety, hemolysis, and particle size were analyzed. Eighty-four eight-week-old male ApoE-mice were randomly divided into blank group (without any treatment), model group (Ang II aortic aneurysm model + tail injection of PBS), control group (modeling + tail injection of Pul-PGEA-pCas9), and experimental group (modeling + tail injection of Pul-PGEA-pCas-sgVs-1), with 21 rats in each group. The incidence, mortality, and maximum diameter of abdominal aortic aneurysm (AAA) and the contents of high sensitivity C-reactive protein (HS-CRP), soluble intercellular adhesion molecule-1 (ICAM-1), soluble vascular cell adhesion molecule-1 (VCAM-1), and TNF-a in serum were compared in different groups of mice. The results showed that Pul-PGEA-pCas-sgVs-1 had good biosafety and transfection ability. The maximum diameter of abdominal aorta, incidence of abdominal aortic aneurysm, mortality, and the expression levels of HS-CRP, ICAM-1, VCAM-1, and TNF-a in the experimental group were lower than those in the model group ( P < 0.05). These results indicated that the plasmid-like nanoparticles Pul-PGEA-pCas-sgVs-1 can inhibit the development of aorta by down-regulating the expression of inflammatory factors, which played a good protective role on the aorta.

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Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Protective effect of vasostatin-1 plasmid-like nanoparticles on aortic aneurysm and its mechanism

Wang

Peng

et al. 2021

Bioengineered

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“…Among the KEGG pathways, we found that metabolic pathways had the most genes. A number of studies have also reported metabolic pathway changes in the aneurysmal wall compared with the normal arterial wall; for example, BAF60a de ciency in vascular smooth muscle cells can prevent the occurrence and progression of AAA by reducing in ammation and extracellular matrix degradation [30]. The ndings from GO enrichment analysis and KEGG pathway analysis in the present study can contribute to the discovery of novel diagnostic indicators and therapeutic targets for AAA.…”

Section: Discussionsupporting

confidence: 59%

Establishment of a Combined Diagnostic Model of Abdominal Aortic Aneurysm with Random Forest and Artificial Neural Network

Duan

Xie

Liu

et al. 2021

Preprint

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Background Abdominal aortic aneurysm (AAA), a disease with high mortality, is limited by the current diagnostic methods in the early screening. This study aimed to construct a diagnostic model for AAA by using a novel machine learning method, i.e., an ensemble of the random forest (RF) algorithm and an artificial neural network (ANN) (RF-ANN), to identify potential AAA-associated genetic biomarkers. Methods Through a search of the Gene Expression Omnibus (GEO) database, two large-sample gene expression datasets (GSE57691 and GSE47472) were identified and downloaded. The differentially expressed genes (DEGs) between the AAA and normal control samples were identified, followed by Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Then, RF-ANN was used to identify the key genes from the DEGs, and an AAA diagnostic model was established. Finally, the diagnostic performance of the model was assessed using the area under the receiver operating characteristic curve (AUC) with GSE47472 as a test dataset. Results Using GSE57691, we obtained 2486 DEGs, 52 biological process annotations, 17 cellular component annotations, 17 molecular function annotations, and 13 significantly enriched KEGG pathways. Out of these DEGs, we further identified 74 key candidate feature genes by using the RF machine learning algorithm. The weight of each key gene was calculated by the ANN with GSE57691 as a training dataset to construct an AAA diagnostic model. A transcription factor (TF) regulatory network of key genes was constructed. Finally, GSE47472 was used to validate the model. The AUC value was 0.786, indicating that the model had a highly satisfactory diagnostic performance. Conclusion Potential AAA-associated gene biomarkers were identified, and a diagnostic model of AAA was established. This study may provide a valuable reference for early clinical diagnosis and the search for therapeutic targets of AAA.

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“…miR-124a serves as a tumor suppressor in several tumors, and miR-124a upregulation can effectively inhibit the life activities such as malignant growth and migration of tumor cells [12]. One research has shown that the levels of miR-124a in the pathological whole blood of the patients are aberrant, suggesting the potential connection between miR-124a and AAA [13]. Nevertheless, the functions of miR-124a on the progression of AAA remain unknown.…”

Section: Introductionmentioning

confidence: 99%

miR-124a Involves in the Regulation of Wnt/β-Catenin and P53 Pathways to Inhibit Abdominal Aortic Aneurysm via Targeting BRD4

et al. 2022

Computational and Mathematical Methods in Medicine

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Background. Abdominal aortic aneurysm (AAA) belongs to a progressive, gradual aortic rupture, which can lead to death without surgical intervention. The key factors regulating the occurrence and progress of AAA are not clear. Increasing studies have indicated that microRNA (miRNA) plays an important role in cancer development. miR-124a serves as a tumor suppressor in several neoplasms, and its upregulation can greatly inhibit the life activities such as malignant growth and migration of tumor cells. Aim. The objective of this study is to explore the association of miR-124a with AAA and to uncover the regulated mechanism of miR-124a on AAA progression. Methods. The specimens from the AAA patients were used for observing the miR-124a expression, and human aortic endothelial cells (hAoECs) were treated with AngII to establish the AAA cell models. The quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), CCK-8, transwell assay, flow cytometry assay, and western blot were conducted to unearth the regulation mechanism of miR-124a on AAA, and the dual-luciferase reporter assay was employed to investigate the downstream target of miR-124a. Results. miR-124a was significantly downregulated in the whole blood of the patients, and the decreased miR-124a was also observed in AAA cell models. Overexpressing miR-124a could effectively inhibit the proliferation and migration and promote the apoptosis of the AAA cells. The dual-luciferase reporter assay confirmed that BRD4 was a downstream target of miR-124a, and BRD4 upregulation could obviously reverse the effects of miR-124a on the phenotype of AAA cells. Moreover, it was found that miR-124a could regulate the activities of Wnt/β-catenin and P53 pathways via targeting the BRD4. Conclusion. Our data suggested that miR-124a could regulate the activities of Wnt/β-catenin and P53 to suppress the AAA progression via targeting the BRD4.

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BAF60a Deficiency in Vascular Smooth Muscle Cells Prevents Abdominal Aortic Aneurysm by Reducing Inflammation and Extracellular Matrix Degradation

Cited by 35 publications

References 54 publications

RETRACTED ARTICLE: Protective effect of vasostatin-1 plasmid-like nanoparticles on aortic aneurysm and its mechanism

RETRACTED ARTICLE: Protective effect of vasostatin-1 plasmid-like nanoparticles on aortic aneurysm and its mechanism

Establishment of a Combined Diagnostic Model of Abdominal Aortic Aneurysm with Random Forest and Artificial Neural Network

miR-124a Involves in the Regulation of Wnt/β-Catenin and P53 Pathways to Inhibit Abdominal Aortic Aneurysm via Targeting BRD4

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