Senescence-associated KRAS upregulation in peripheral T cells links to premature coronary artery disease
Aims: Premature coronary artery disease (PCAD) lacks specific molecular drivers, and the role of immunosenescence is unclear. We investigated whether aging-related gene dysregulation in T cells contributes to PCAD. Methods: We combined bulk transcriptomics of PBMCs from 12 PCAD patients and 21 controls, single-cell RNA sequencing of PBMCs and human atherosclerotic plaques, weighted gene…
Premature coronary artery disease (PCAD) may be linked to age-related gene dysregulation in T cells, according to a recent study. The researchers investigated whether changes in T cell genes associated with aging could contribute to PCAD. Using various molecular biology techniques, they identified the KRAS gene as a key player in this connection.
KRAS was found to be upregulated in effector CD8+ T cells, which are the cells most prone to aging-related senescence. These senescent T cells also showed higher levels of KRAS. The study's findings suggest that KRAS-high effector CD8+ T cells are present in coronary and carotid plaques, which are common in PCAD. These cells display enhanced cytotoxicity, exhaustion, and senescence features.
The researchers also used a computational approach to predict a small molecule that could potentially bind to inactive KRAS. This discovery could lead to a new biomarker for PCAD and a potential therapeutic target for further research.
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