Matrix metalloproteinases are regulated by MicroRNA 320 in macrophages and are associated with aortic dissection

Liao, Min; Zou, Sili; Bao, Yan; Jin, Jie; Yang, Junlin; Liu, Yandong; Green, Mark; Yang, Futang; Qu, Lefeng

doi:10.1016/j.yexcr.2018.06.011

Cited by 21 publications

(15 citation statements)

References 14 publications

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“…Overexpression of miR-30a promotes the progression of AD, possibly by targeting lysyl oxidase (7). MiR-320 could downregulate the expression of MMPs by macrophages in AD patients (8). MiR-21 knockout aggravated AngII-induced thoracic aortic dissection formation in mice, which was related to the dysfunction of TGF-β signaling (9).…”

Section: Introductionmentioning

confidence: 99%

Identification of the molecular mechanisms associated with acute type A aortic dissection through bioinformatics methods

Jiang

2019

Braz J Med Biol Res

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Aortic dissection is characterized by the redirection of blood flow, which flows through an intimal tear into the aortic media. The purpose of this study was to find potential acute type A aortic dissection (AAAD)-related genes and molecular mechanisms by bioinformatics. The gene expression profiles of GSE52093 were obtained from Gene Expression Omnibus (GEO) database, including 7 AAAD samples and 5 normal samples. The differentially expressed genes (DEGs) were detected between AAAD and normal samples. The functional annotation and pathway enrichment analysis were conducted through the Database for Annotation, Visualization and Integration Discovery (DAVID). A protein-protein interaction network was established by the Search Tool for the Retrieval of Interacting Genes (STRING) software. The microRNAs (miRNAs) of these differentially expressed genes were predicted using omicroRNA.org4 database. Moreover, DEGs were analyzed in the comparative toxicogenomics (CTD) database to screen out the potential therapeutic small molecules. As a result, there were 172 DEGs identified in patients with AAAD. These DEGs were significantly enriched in 6 pathways, including cell cycle, oocyte meiosis, DNA replication, extracellular matrix-receptor interaction, and mineral absorption pathway. Notably, CDC20, CDK1, CHEK1, KIF20A, MCM10, PBK, PTTG1, RACGAP, and TOP2A were crucial genes with a high degree in the proteinprotein interaction network. Furthermore, potential miRNAs (miR-301, miR-302 family, and miR-130 family) were identified. In addition, small molecules like azathioprine and zoledronic acid were identified to be potential drugs for AAAD.

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Section: Introductionmentioning

confidence: 99%

Identification of the molecular mechanisms associated with acute type A aortic dissection through bioinformatics methods

Jiang

2019

Braz J Med Biol Res

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“…Of these candidate genes, 4 (MMP2, WNT1, IGF1R and BCL2) are potentially involved in the pathogenesis of TAD. Aortic aneurysm, which refers to the focal dilation of the aorta, results from impaired integrity of the aortic ECM (23,24). MMPs, traditionally known as ECM-degrading enzymes, have been demonstrated to have an important role in the myocardial remodeling process; for instance, these enzymes are active in dilated failing hearts (25).…”

Section: Discussionmentioning

confidence: 99%

Efficient detection of differentially methylated regions in the genome of patients with thoracic aortic dissection and association with MMP2 hypermethylation

Lin¹,

Zhou

Zheng

et al. 2020

Exp Ther Med

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DNA methylation is known to regulate the expression of numerous genes but its role in the pathogenesis of thoracic aortic dissection (TAD) has remained largely elusive. In the present study, the DNA methylome of patients with TAD was analyzed using a methylation microarray and bisulfite pyrosequencing was used to determine whether the hypermethylation of matrix metalloproteinase 2 (MMP2) specifically is associated with TAD. Chip-based whole-DNA methylome analysis was performed on 4 male patients with TAD and 4 male healthy controls using an Illumina HumanMethylation EPIC 850K BeadChip. The resulting data were analyzed by clustering and principal component analysis, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on the differentially methylated genes to interrogate their biological functions. Compared to the healthy controls, 3,362 loci were differentially methylated in the patients with TAD with a statistical significance of P<0.05, while 1,223 loci had a significance of P<0.01. Among these loci, 2,019 were hypermethylated and 1,343 were hypomethylated. From GO analysis within the biological process category, the MMP2, MMP14 and WNT2B genes were identified. enrichment was observed for loci involved in cellular component organization, enzyme-linked receptor protein signaling pathways (potentially having a key role in the development of cardiopulmonary function disorders) and vascular reconstruction. Bisulfite pyrosequencing of plasma samples indicated significantly increased methylation (P<0.01) of the CpG site at position 2 in the promoter of MMP2 in the TAD group relative to the healthy controls, and the mean methylation level of four CpG sites on the MMP2 gene in the TAD group was slightly higher than that in the control group, but not significantly. Hypermethylation of the MMP2 promoter may be a promising novel diagnostic and prognostic biomarker for TAD. Future studies on the epigenetics of biomarkers linked to vascular reconstruction and immune function may provide further insight into the pathogenesis and progression of TAD.

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“…In fact, overexpressed miR-320 was able to inhibit MMP secretion. A recent study indicated that low miR-320 expression leads to insufficient suppression of MMP secretion, leading to higher expression of MMPs, aggravated ECM destruction, and increased risk of AD (Liao et al, 2018).…”

Section: Macrophage-associated Factors That Protect Against Admentioning

confidence: 99%

The Role of Macrophages in Aortic Dissection

et al. 2020

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Aortic dissection (AD) is a fatal disease that accounts for a large proportion of aorticrelated deaths and has an incidence of about 3-4 per 100,000 individuals every year. Recent studies have found that inflammation plays an important role in the development of AD, and that macrophages are the hub of inflammation in the aortic wall. Aortic samples from AD patients reveal a large amount of macrophage infiltration. The sites of macrophage infiltration and activity vary throughout the different stages of AD, with involvement even in the tissue repair phase of AD. Angiotensin II has been shown to be an important factor in the stimulation of macrophage activity. Stimulated macrophages can secrete metalloproteinases, inflammatory factors and other substances to cause matrix destruction, smooth muscle cell apoptosis, neovascularization and more, all of which destroy the aortic wall structure. At the same time, there are a number of factors that regulate macrophages to reduce the formation of AD and induce the repair of torn aortic tissues. The aim of this review is to take a close look at the roles of macrophages throughout the course of AD disease.

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Matrix metalloproteinases are regulated by MicroRNA 320 in macrophages and are associated with aortic dissection

Cited by 21 publications

References 14 publications

Identification of the molecular mechanisms associated with acute type A aortic dissection through bioinformatics methods

Identification of the molecular mechanisms associated with acute type A aortic dissection through bioinformatics methods

Efficient detection of differentially methylated regions in the genome of patients with thoracic aortic dissection and association with MMP2 hypermethylation

The Role of Macrophages in Aortic Dissection

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