T cell KRAS upregulation is linked to premature coronary disease

In human blood and tissue samples, researchers investigated whether aging-related gene dysregulation in T cells contributes to premature coronary artery disease. The preprint evaluated bulk transcriptomics from peripheral blood mononuclear cells of 12 patients and 21 controls, alongside single-cell RNA sequencing of blood cells and coronary and carotid atherosclerotic plaques. Through gene co-expression network analysis, the authors identified KRAS as a hub gene intersecting disease-associated and aging-related genes. Single-cell analysis showed KRAS upregulation predominantly in effector CD8+ T cells, which had the highest senescence scores that were further elevated in disease. KRAS-high effector CD8+ T cells were also detected in plaques, displaying enhanced cytotoxicity, exhaustion, and senescence features. Network perturbation of KRAS impacted the cell killing pathway, and molecular docking computationally predicted a candidate small molecule that binds inactive KRAS.