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<p>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 senescence-associated-β-galactosidase activity, nuclear enlargement, and increased Cyclin dependent kinase inhibitor 1&#xa0;A 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 pro-atherogenic phenotypes in HCAECs in vitro. Importantly, mTOR inhibition is identified as a promising strategy to counteract radiation-associated endothelial dysfunction. This work positions senescence as a tractable therapeutic target in radiation-induced vascular injury.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月30日

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  • Christopher Whiteman

摘要

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 senescence-associated-β-galactosidase activity, nuclear enlargement, and increased Cyclin dependent kinase inhibitor 1 A 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 pro-atherogenic phenotypes in HCAECs in vitro. Importantly, mTOR inhibition is identified as a promising strategy to counteract radiation-associated endothelial dysfunction. This work positions senescence as a tractable therapeutic target in radiation-induced vascular injury.