Inflammation-Induced Alternative Splicing in Human Endothelial Cells Reveals Genetic Mechanisms of Cardiovascular Disease Risk.

ABSTRACT: Alternative splicing modulates mRNA protein-coding sequence, stability, and translation rates, although it has not been comprehensively annotated in human endothelial cells (ECs). EC dysfunction is a hallmark of complex inflammatory diseases, including cancer and atherosclerosis. Therefore, this study modeled acute inflammation in vitro using 53 genetically distinct human aortic EC lines exposed to interleukin-1β (IL-1β) or control media. This approach identified 1,224 differentially spliced transcripts (DSTs) between IL-1β and control conditions. DSTs were enriched for alternative first (AF) exons, including several novel mRNA isoforms of disease-associated and metabolic genes. It was hypothesized and confirmed that AF splicing was driven by alternative promoters using ATAC-seq and ChIP-s

SUBMITTER: Golebiewski AK 

PROVIDER: S-EPMC12324277 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature