Purine metabolic adaptation protects the endothelium from disturbed flow–induced DNA damage and atherosclerosis
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.
Authors
- Yaqi Zhou (ORCID: https://orcid.org/0000-0003-0615-6631)
- Qiuhua Yang (ORCID: https://orcid.org/0000-0002-5582-3771)
- Hanjoong Jo (ORCID: https://orcid.org/0000-0003-1833-372X)
- Yuqing Huo (ORCID: https://orcid.org/0000-0002-0305-4122)
- Dingwei Zhao
- Yongfeng Cai
- Tammy Lu
- Yuan Zhao (ORCID: https://orcid.org/0000-0002-7045-138X)
- Wendy Zhang (ORCID: https://orcid.org/0000-0002-3586-2626)
- Zhidan Zhang
- Qian Ma
- Tohru Fukai
- Yiming Xu
- Peishan Xu
- Varadarajan Sudhahar
Institutions
- Guangzhou University of Chinese Medicine (CN)
- Georgia Institute of Technology (US)
- Baylor College of Medicine (US)
- Anhui Medical University (CN)
- Augusta University (US)
- The Wallace H. Coulter Department of Biomedical Engineering (US)
- Rowan University (US)
- Stony Brook University (US)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- Proceedings of the National Academy of Sciences
- Published
- 2026-04-30
- DOI
- https://doi.org/10.1073/pnas.2526299123
- Primary Topic
- Adenosine and Purinergic Signaling
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- American Heart Association
- National Institutes of Health