What question did this study set out to answer?

Investigate how purine metabolism protects endothelial cells from DNA damage and atherosclerosis.

May 3, 2026

Purine metabolic adaptation protects the endothelium from disturbed flow-induced DNA damage and atherosclerosis.

Key Points

Investigate how purine metabolism protects endothelial cells from DNA damage and atherosclerosis.
Deleted specific genes to assess their impact on DNA damage and atherogenesis.
Applied purine-base supplementation to evaluate repair capabilities.
Identified MYC as a regulator in the d-flow-MYC-ATIC-DNPS axis.
Deletion leads to increased DNA damage and accelerated atherosclerosis.
Purine-base supplementation significantly improves DNA repair mechanisms.
MYC drives the induction of ATIC, which supports nucleotide sufficiency.

Abstract

deletion exacerbates DNA damage, apoptosis, barrier dysfunction, and accelerates atherogenesis, while purine-base supplementation rescues repair defects. We further identify MYC as a mechanosensitive driver of ATIC induction. These findings establish a d-flow-MYC-ATIC-DNPS axis that sustains nucleotide sufficiency for DNA repair and maintains endothelial barrier integrity, suggesting potential endothelial-targeted therapeutic strategies for atherosclerosis.

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