Senescence inhibition by rapamycin mitigates radiation-induced atherosclerotic characteristics in human coronary endothelial cells

Ionising radiation (IR) is a recognised risk factor for cardiovascular disease (CVD), yet the mechanisms linking it to exposure remain incompletely understood. We show that IR drives a pro-atherogenic phenotype in human coronary artery endothelial cells (HCAECs) through the induction of cellular senescence, and that rapamycin attenuates these effects. IR triggered hallmark senescence features, including elevated SA-β-galactosidase activity, nuclear enlargement, and increased CDKN1A and p53 expression. Functionally, irradiated HCAECs displayed impaired barrier integrity and heightened monocyte adhesion. Transcriptomic and proteomic profiling revealed broad IR-induced alterations enriched in DNA damage response, cell-cycle arrest, senescence, proteostasis, and immune-related pathways. These findings establish a mechanistic link between radiation-induced endothelial senescence and early atherogenic-associated dysfunction, demonstrating that senescence is a driver of vascular injury. Importantly, identifying mTOR inhibition as a promising strategy to counteract radiation-associated endothelial dysfunction. This work positions senescence as a tractable therapeutic target in radiation-induced vascular injury.