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Medicine for Atherosclerotic Diseases of Zhejiang Province","award":["PPXK2018-04"],"award-info":[{"award-number":["PPXK2018-04"]}]},{"name":"Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province","award":["2022020304"],"award-info":[{"award-number":["2022020304"]}]},{"name":"Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province","award":["2022E10026"],"award-info":[{"award-number":["2022E10026"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>We explored metastasis-associated protein 1 (MTA1) promoter methylation in the development of brain arteriovenous malformation (BAVM). The clinical data of 148 sex- and age-matched BAVMs and controls were collected, and the MTA1 DNA methylation in peripheral white blood cells (WBC) was assessed by bisulfite pyrosequencing. Among them, 18 pairs of case\u2013control samples were used for WBC mRNA detection, 32 pairs were used for WBC MTA1 protein measurement, and 50 pairs were used for plasma inflammatory factor analysis. Lipopolysaccharide (LPS) treatment was used to induce an inflammatory injury cell model of human brain microvascular endothelial cells (BMECS). 5-Aza-2\u2032-deoxycytidine (5-AZA), nicotinic acid (NA), and MTA1 siRNAs were used in functional experiments to examine BMECS behaviors. RT-qPCR, Western blot, and ELISA or cytometric bead arrays were used to measure the expression levels of MTA1, cytokines, and signaling pathway proteins in human blood or BMECS. The degree of MTA1 promoter methylation was reduced in BAVM compared with the control group and was inversely proportional to MTA1 expression. Plasma ApoA concentrations in BAVM patients were significantly lower than those in controls and correlated positively with MTA1 promoter methylation and negatively with MTA1 expression. The expression of cytokine was markedly higher in BAVM than in controls. Cell experiments showed that 5-AZA decreased the methylation level of MTA1 and increased the expression of MTA1 protein. LPS treatment significantly increased cytokine concentrations (p &lt; 0.05). NA and MTA1 silencing could effectively reverse the LPS-mediated increase in IL-6 and TNF-\u03b1 expression through the NF-\u03baB pathway. Our study indicated that NA may regulate MTA1 expression by affecting promoter DNA methylation, improve vascular inflammation through the NF-\u03baB pathway, and alleviate the pathological development of BAVM.<\/jats:p>","DOI":"10.3390\/biom13101495","type":"journal-article","created":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T05:07:13Z","timestamp":1696828033000},"page":"1495","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Nicotinic Acid-Mediated Modulation of Metastasis-Associated Protein 1 Methylation and Inflammation in Brain Arteriovenous Malformation"],"prefix":"10.3390","volume":"13","author":[{"given":"Xinpeng","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Ningbo University, Ningbo 315010, China"},{"name":"Department of Neurosurgery, Ningbo Hospital of Zhejiang University, Ningbo 315010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengjun","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Ningbo University, Ningbo 315010, China"},{"name":"Department of Neurosurgery, Ningbo Hospital of Zhejiang University, Ningbo 315010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziliang","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Ningbo University, Ningbo 315010, China"},{"name":"Cixi Biomedical Research Institute, Wenzhou Medical University, Cixi 315302, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanyong","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Ningbo University, Ningbo 315010, China"},{"name":"Department of Neurosurgery, Ningbo Hospital of Zhejiang University, Ningbo 315010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Ningbo University, Ningbo 315010, China"},{"name":"Department of Neurosurgery, Ningbo Hospital of Zhejiang University, Ningbo 315010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenhui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Ningbo University, Ningbo 315010, China"},{"name":"Department of Neurosurgery, Ningbo Hospital of Zhejiang University, Ningbo 315010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenting","family":"Lan","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital of Ningbo University, Ningbo 315010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Ningbo University, Ningbo 315010, China"},{"name":"Department of Neurosurgery, Ningbo Hospital of Zhejiang University, Ningbo 315010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3598-9747","authenticated-orcid":false,"given":"Yi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Ningbo University, Ningbo 315010, China"},{"name":"Department of Neurosurgery, Ningbo Hospital of Zhejiang University, Ningbo 315010, China"},{"name":"Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, Ningbo 315010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2704","DOI":"10.1056\/NEJMcp067192","article-title":"Clinical practice. 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