| Title: | Food-derived chlorogenic acid prevents aortic aneurysm and dissection by nutritional restore branched-chain amino acid dyshomeostasis |
| Journal: | The Journal of Nutritional Biochemistry |
| Published: | 6 Dec 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41360205/ |
| DOI: | https://doi.org/10.1016/j.jnutbio.2025.110211 |
Publication 16773
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Abstract
Aortic aneurysm and dissection (AAD) is a life-threatening cardiovascular disorder with no currently available targeted therapies, underscoring the critical need for effective preventive strategies. Through integrative analysis of the UK Biobank and FooDB databases, we identified chlorogenic acid (CGA)--a natural polyphenol abundant in coffee and tea--as a potential protective compound against AAD. Using two mouse models of AAD: β-aminopropionitrile (BAPN) plus angiotensin II (Ang II) in 4-week-old wild-type mice and erythropoietin (EPO)-induced AAD in 8-week-old wild-type mice, we demonstrated that CGA administration significantly reduced AAD incidence, mortality, and aortic wall damage. Mechanistically, we discovered that the large neutral amino acid transporter 3 (LAT3) plays a pivotal role in AAD pathogenesis by mediating excessive branched-chain amino acids (BCAAs) uptake into vascular smooth muscle cells (SMCs). Dysregulated BCAAs metabolism led to intracellular BCAAs accumulation and hyperactivation of the mTOR signaling pathway, driving SMCs reprogramming and promoting AAD development. Crucially, CGA directly targeted and inhibited LAT3, thereby normalizing BCAA metabolism and suppressing mTOR activity, which mitigated AAD progression. Our findings not only reveal the therapeutic potential of CGA in AAD prevention but also identify the LAT3/BCAA/mTOR axis as a novel mechanistic target for AAD intervention.</p>
14 Authors
- Zhen-Xiao Ma
- Ze-Qun Yin
- Zi-An Feng
- Xiang-Peng Xie
- Ao Li
- Shi-Hao Fu
- Qi Yue
- Sheng Wang
- Li-Kun Ma
- Ya-Jun Duan
- Dan-Qing He
- Jun-Fang Wu
- Shuang Zhang
- Zhi-Wei Zhao
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