Senescent CD8 T cells show elevated KRAS in premature coronary artery disease
Analyses of human blood and plaque samples link KRAS-driven immunosenescence and cell cytotoxicity to early cardiovascular disease.
bioRxiv · Sun Z et al. · Paper published 28 Sep 2026
In a preprint analyzing human blood and plaque samples, researchers investigated whether aging-related gene dysregulation in T cells drives premature coronary artery disease. The team profiled peripheral blood mononuclear cells from 12 patients with premature coronary artery disease and 21 controls using bulk transcriptomics. They integrated these data with single-cell RNA sequencing from blood and atherosclerotic plaques, network analyses, and molecular docking. KRAS emerged as a hub gene intersecting disease-associated and aging-related genes. Single-cell analysis revealed that KRAS was upregulated mainly in effector CD8+ T cells. These cells had the highest senescence scores, which rose further in disease. In network perturbation models, KRAS strongly impacted cell killing pathways. KRAS-high effector CD8+ T cells appeared in coronary and carotid plaques, displaying enhanced cytotoxicity, exhaustion, and senescence features. Computational docking also identified a candidate small molecule predicted to bind inactive KRAS.
Why it matters
The findings bridge immunosenescence and cardiovascular pathology by highlighting senescent, cytotoxic T cells as potential drivers of early plaque development. They point to KRAS as a prospective biomarker and target for interventions against age-accelerated arterial disease.
Caveats
This observational study is a preprint that analyzed a small cohort of 33 human participants. The findings are primarily computational and network-based, requiring experimental and functional validation in future studies.
Written from the paper’s abstract, and every claim checked against it before publishing. Read the paper for the full methods and data.
The paper
Senescence-associated KRAS upregulation in peripheral T cells links to premature coronary artery disease
Sun Z, Yang Z, Wang X et al.
bioRxiv · 28 Sep 2026 · Preprint, not yet peer-reviewed
- Relevance
- Relevant
- News value
- Notable
- Evidence
- Humans
- Status
- Preprint
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