{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE300nnn/GSE300982/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Mus musculus"],"gds_type":["Genome binding/occupancy profiling by high throughput sequencing"," Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE300982"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Chronic Electronic Cigarette Exposure Promotes Atherosclerosis and Chondrogenic Modulation of Smooth Muscle Cells","description":"Electronic cigarettes (E-cigs) represent a rapidly growing public health concern, particularly due to their widespread adoption among adolescents. Recent epidemiological and experimental evidence has linked E-cig use to accelerated atherosclerosis, though the underlying mechanisms remain incompletely understood. Here, we investigated how E-cig exposure promotes atherosclerotic lesion formation and vascular remodeling through phenotypic modulation of vascular smooth muscle cells (SMCs). We utilized SMC lineage-tracing mice crossed onto an ApoE-null hyperlipidemic background and exposed them to pod-based E-cigs (Juul) three times weekly over a 12-week period (n=16 per group), comparing results to control mice exposed to Ambient air. Single-cell RNA sequencing (scRNA-seq) and assay for transposase-accessible chromatin sequencing (scATAC-seq) were conducted on cells isolated from the aortic sinus, complemented by histological assessment of osteogenic markers. Our analyses revealed a significant shift in SMC phenotype toward a chondrogenic lineage (CMC) in e-cigarette-exposed mice, evidenced by markedly increased expression of chondrogenic markers Col2a1 and Tnfrsf11b. Correspondingly, histological evaluations demonstrated increased osteogenic activity in E-cig-exposed animals. Chromatin accessibility profiling further identified a unique cellular cluster enriched for glutamatergic signaling pathways, particularly showing enhanced accessibility at Grin2a, a gene encoding the NMDA receptor subunit GluN2A. Notably, GRIN2A expression was upregulated in HCASMCs upon e-cigarette exposure, and the observed E-cig-induced phenotypic modulation was found to be GRIN2A-dependent, suggesting a robust gene-environment interaction. Collectively, these findings elucidate critical mechanistic pathways through which e-cigarette exposure promotes atherosclerosis, underscoring GRIN2A as a potential therapeutic target to address cardiovascular risks associated with electronic nicotine delivery systems.","dates":{"publication":"2026/06/26"},"accession":"GSE300982","cross_references":{"GSM":["GSM9073043","GSM9073032","GSM9073042","GSM9073041","GSM9073040","GSM9073047","GSM9073036","GSM9073046","GSM9073035","GSM9073045","GSM9073034","GSM9073044","GSM9073033","GSM9073039","GSM9073038","GSM9073037"],"GPL":["24247"],"GSE":["300982"],"taxon":["Mus musculus"]}}