Full-Length Transcriptome Profiling Reveals Extensive Remodeling of mRNA Isoforms and Post-Transcriptional Networks in Cigarette Smoke-Exposed Human Aortic Smooth Muscle Cells
Cigarette smoke extract (CSE) demonstrates paradoxical concentration-dependent effects on vascular smooth muscle cells, though the underlying isoform-level mechanisms remain unexplored. We employed Oxford Nanopore long-read sequencing to analyze the full-length transcriptome of human aortic smooth muscle cells following CSE treatment (0.2%-0.8%). We confirmed low-concentration CSE (0.2%) slightly promoted viability while higher concentrations (0.4%-0.8%) induced dose-dependent suppression. Sequencing of 0.6% CSE-treated cells revealed 11,222 novel transcripts and extensive post-transcriptional reprogramming, including: 1,866 upregulated transcripts involving ferroptosis and cell division; 493 downregulated transcripts in oxidative phosphorylation and glutathione metabolism; 1,753 alternative polyadenylation events mediating 3'UTR remodeling; and 269 alternative splicing events affecting cell cycle regulators and transcription factors (CREM, FOSL1). Our study establishes that high-concentration CSE cytotoxicity is executed through coordinated post-transcriptional dysregulation, providing the first isoform-level perspective on smoking-induced vascular pathology and revealing previously unrecognized regulatory mechanisms in cigarette smoke-mediated vascular damage.