{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE301nnn/GSE301109/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301109"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"SIRT7 regulates smooth muscle phenotypic switching by deacetylating SRF to repress abdominal aortic aneurysm formation","description":"Abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular disease for which there are no effective pharmacological treatments. Histone deacetylases (HDACs) have gained increasing recognition as critical regulators of the pathological processes of various cardiovascular diseases. However, the role of HDACs in AAA formation remains largely unexplored. Here, we reported that SIRT7 exhibited the most pronounced downregulation among all 18 HDACs in human AAA tissues. Global Sirt7 knockout exacerbated AAA formation, and RNA sequencing revealed that SIRT7 deficiency promoted VSMC phenotypic switching. Subsequent VSMC-specific SIRT7 knockout confirmed the exacerbation of aortic dilation, whereas SIRT7 overexpression inhibited AAA progression. Mechanistically, SIRT7-mediated deacetylation of serum response factor (SRF) at K154 maintained SRF transcriptional activity, suppressed its nuclear-to-cytoplasmic translocation and ubiquitin-dependent degradation, and preserved the VSMC contractile phenotype. Pathologically, SIRT7 deficiency increased SRF acetylation, accelerated its protein degradation, and exacerbated VSMC phenotypic switching, thereby promoting AAA formation. Pharmacological activation of SIRT7 using nicotinamide mononucleotide (NMN), a precursor of NAD+ biosynthesis, inhibited VSMC phenotypic switching and therapeutically attenuated aortic dilation. Collectively, our findings reveal the intricate mechanisms underlying SIRT7-mediated SRF K154 deacetylation to inhibit AAA progression. Importantly, NMN supplementation may be an effective therapeutic strategy for AAA.","dates":{"publication":"2026/09/15"},"accession":"GSE301109","cross_references":{"GSM":["GSM9075527","GSM9075528","GSM9075529","GSM9075530","GSM9075531","GSM9075532"],"GPL":["34290"],"GSE":["301109"],"taxon":["Mus musculus"],"PMID":["[42420530]"]}}