Excessive DNA damage mediates ECM degradation via the RBBP8/NOTCH1 pathway in sporadic aortic dissection

Zhou, Ze-Hua; Liu, Yan; Gao, Shan; Qi, Feiran; Ding, Ningyu; Zhang, Junmeng; Li, Ruisha; Wang, Junxia; Shi, Jian; Yu, Ronghuang; Wang, Yali; Li, Yulin; Pan, Jun; Du, Jie; Wang, Dongjin

doi:10.1016/j.bbadis.2021.166303

Cited by 12 publications

(8 citation statements)

References 64 publications

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“…The mutations in this gene were correlated with aortic aneurysm and dissection[ 22 , 23 ]. Inhibition of NOTCH1 promoted β-aminopropionitrile-induced AD formation[ 24 ]. LOXL2 was a hypomethylated position-associated gene related to cg24531955 and was found upregulated in AAD[ 25 ].…”

Section: Resultsmentioning

confidence: 99%

DNA methylation alternation in Stanford- A acute aortic dissection

Chen

et al. 2022

BMC Cardiovasc Disord

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Background Acute aortic dissection (AAD) is a life-threatening cardiovascular disease. Recent studies have shown that DNA methylation may be associated with the pathological mechanism of AAD, but the panorama of DNA methylation needs to be explored. Methods DNA methylation patterns were screened using Infinium Human Methylation 450 K BeadChip in the aortic tissues from 4 patients with Stanford-A AAD and 4 controls. Gene enrichment was analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene ontology (GO). DNA methylation levels of candidate genes were determined by pyrosequencing in the replication cohort including 16 patients with AAD and 7 controls. Protein expression level of candidate gene was assessed by Western blot. Results A total of 589 differentially methylated positions including 315 hypomethylated and 274 hypermethylated positions were found in AAD group. KEGG analysis demonstrated that differentially methylated position-associated genes were enriched in MAPK signaling pathway, TNF signaling pathway and apoptosis pathway, et al. GO analysis demonstrated that differentially methylated position-associated genes were enriched in protein binding, angiogenesis and heart development et al. The differential DNA methylation in five key genes, including Fas, ANGPT2, DUSP6, FARP1 and CARD6, was authenticated in the independent replication cohort. The protein expression level of the Fas was increased by 1.78 times, indicating the possible role of DNA methylation in regulation of gene expression. Conclusion DNA methylation was markedly changed in the aortic tissues of Stanford-A AAD and associated with gene dysregulation, involved in AAD progression.

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Section: Resultsmentioning

confidence: 99%

DNA methylation alternation in Stanford- A acute aortic dissection

Chen

et al. 2022

BMC Cardiovasc Disord

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“…At the same time, morphological changes in endothelial cells in AAD patients, such as endothelial cell hyperplasia, loose cell junctions, and endothelial cell desquamation in aortic segments, suggest that endothelial cells are damaged in AAD patients, which may likewise underlie the pathogenesis of AAD ( 107 ). Interestingly, RBBP8/NOTCH1 was found to act as a linking molecule between DNA damage/repair and extracellular matrix (ECM) tissue, and we speculate that excessive DNA damage is a characteristic pathological change in sporadic aortic dissection ( 116 ), which may be associated with massive cellular damage and degeneration.…”

Section: Discovery Of Aad Biomarkers Based On Multi-omics Technologiesmentioning

confidence: 98%

Applying multi-omics techniques to the discovery of biomarkers for acute aortic dissection

Hao

Cheng

Jiang

et al. 2022

Front. Cardiovasc. Med.

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Acute aortic dissection (AAD) is a cardiovascular disease that manifests suddenly and fatally. Due to the lack of specific early symptoms, many patients with AAD are often overlooked or misdiagnosed, which is undoubtedly catastrophic for patients. The particular pathogenic mechanism of AAD is yet unknown, which makes clinical pharmacological therapy extremely difficult. Therefore, it is necessary and crucial to find and employ unique biomarkers for Acute aortic dissection (AAD) as soon as possible in clinical practice and research. This will aid in the early detection of AAD and give clear guidelines for the creation of focused treatment agents. This goal has been made attainable over the past 20 years by the quick advancement of omics technologies and the development of high-throughput tissue specimen biomarker screening. The primary histology data support and add to one another to create a more thorough and three-dimensional picture of the disease. Based on the introduction of the main histology technologies, in this review, we summarize the current situation and most recent developments in the application of multi-omics technologies to AAD biomarker discovery and emphasize the significance of concentrating on integration concepts for integrating multi-omics data. In this context, we seek to offer fresh concepts and recommendations for fundamental investigation, perspective innovation, and therapeutic development in AAD.

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“…Importantly, ECM degradation is controlled by zinc-containing endopeptidases including matrix metalloproteinases and a disintegrin and metalloproteinase proteins with thrombospondin motifs (ADAMTSs) [ 214 , 215 ]. Excessive ECM degradation can lead to an abnormal ECM characterized by unbalanced ECM components or ECM components that are not crosslinked properly [ 216 , 217 ]. The occurrence of more ECM degradation than synthesis can result in the removal of whole tissue components such as that of basement membranes and the vasculature, allowing cells to migrate in an uncontrolled manner [ 218 , 219 , 220 ].…”

Section: Proteolytic Degradation Of the Extracellular Matrixmentioning

confidence: 99%

The Extracellular Matrix: Its Composition, Function, Remodeling, and Role in Tumorigenesis

Dzobo

Dandara

2023

Biomimetics

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The extracellular matrix (ECM) is a ubiquitous member of the body and is key to the maintenance of tissue and organ integrity. Initially thought to be a bystander in many cellular processes, the extracellular matrix has been shown to have diverse components that regulate and activate many cellular processes and ultimately influence cell phenotype. Importantly, the ECM’s composition, architecture, and stiffness/elasticity influence cellular phenotypes. Under normal conditions and during development, the synthesized ECM constantly undergoes degradation and remodeling processes via the action of matrix proteases that maintain tissue homeostasis. In many pathological conditions including fibrosis and cancer, ECM synthesis, remodeling, and degradation is dysregulated, causing its integrity to be altered. Both physical and chemical cues from the ECM are sensed via receptors including integrins and play key roles in driving cellular proliferation and differentiation and in the progression of various diseases such as cancers. Advances in ‘omics’ technologies have seen an increase in studies focusing on bidirectional cell–matrix interactions, and here, we highlight the emerging knowledge on the role played by the ECM during normal development and in pathological conditions. This review summarizes current ECM-targeted therapies that can modify ECM tumors to overcome drug resistance and better cancer treatment.

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Excessive DNA damage mediates ECM degradation via the RBBP8/NOTCH1 pathway in sporadic aortic dissection

Cited by 12 publications

References 64 publications

DNA methylation alternation in Stanford- A acute aortic dissection

DNA methylation alternation in Stanford- A acute aortic dissection

Applying multi-omics techniques to the discovery of biomarkers for acute aortic dissection

The Extracellular Matrix: Its Composition, Function, Remodeling, and Role in Tumorigenesis

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