GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE300nnn/GSE300982/primary200OKGenomicsMus musculusGenome binding/occupancy profiling by high throughput sequencing Expression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE300982GEOGSEfalseChronic Electronic Cigarette Exposure Promotes Atherosclerosis and Chondrogenic Modulation of Smooth Muscle CellsElectronic 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.2026/06/26GSE300982GSM9073043GSM9073032GSM9073042GSM9073041GSM9073040GSM9073047GSM9073036GSM9073046GSM9073035GSM9073045GSM9073034GSM9073044GSM9073033GSM9073039GSM9073038GSM907303724247300982Mus musculus