Abstract: FR-PO400
Tryptophan Metabolite 3-Hydroxy Anthranilic Acid Decreases CKD-Associated Atherosclerosis
Session Information
- Hypertension and CVD: Basic
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1601 Hypertension and CVD: Basic
Authors
- Chai, Biaoxin, University of Michigan Medical School, Ann Arbor, Michigan, United States
- Meza, Julian, University of Michigan, Ann Arbor, Michigan, United States
- Berthier, Celine C., University of Michigan Medical School, Ann Arbor, Michigan, United States
- Eichinger, Felix H., University of Michigan Medical School, Ann Arbor, Michigan, United States
- Byun, Jaeman, University of Michigan Medical School, Ann Arbor, Michigan, United States
- Mathew, Anna Vachaparampil, University of Michigan Medical School, Ann Arbor, Michigan, United States
Background
The tryptophan catabolism pathway is upregulated in chronic kidney disease (CKD), and tryptophan metabolite 3-hydroxy anthranilic acid (3-HAA) is an anti-inflammatory metabolite that has been shown to decrease atherosclerosis in preclinical and clinical models. However, the mechanistic link between 3-HAA and CKD accelerated atherosclerosis is unknown.
Methods
Twenty-four male LDLr-/- mice underwent 5/6 nephrectomy (CKD) and were placed on a high-fat/high-cholesterol diet (HFD) for 16 weeks. 3-HAA (200 mg/g) was injected intraperitoneally three times a week (3-HAA mice, n=12), while controls (n=12) were injected with PBS for 16 weeks. We quantified atherosclerosis with Oil Red-O staining of en face aortic sections at the end of 16 weeks. We used human macrophage cultures that were treated with 10µM 3-HAA and measured changes in transcriptome profiles and macrophage functions like apoptosis, phagocytosis, and cytokine profiles.
Results
3-HAA treatment increased 3-HAA levels which negatively correlated with aortic atherosclerotic lesions in 3-HAA mice. 3-HAA treatment decreased IL-6 levels and increased IL-10 levels. 3-HAA treatment of human macrophages influences nitric oxide, platelet-derived growth factor, and CXCR3 signaling, while 3-HAA treatment had no effect on T cells. Activated human macrophage cultures reveal that 3-HAA treatment decreases macrophage apoptosis and increases phagocytosis.
Conclusion
In summary, 3-HAA treatment decreases CKD-associated atherosclerosis by its action on macrophage apoptosis, phagocytosis, cytokine profiles, and inflammatory signaling.
Funding
- Other NIH Support