Abstract: TH-PO0284
Anti-Inflammatory Response of Asymptomatic Hyperuricemia in Salt-Sensitive Hypertension
Session Information
- Hypertension and CVD: Mechanisms
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1601 Hypertension and CVD: Basic
Authors
- Shapiro, Abigail, University of South Florida, Tampa, Florida, United States
- Dissanayake, Lashodya Vindana, University of South Florida, Tampa, Florida, United States
- Levchenko, Vladislav, University of South Florida, Tampa, Florida, United States
- Palygin, Oleg, Medical University of South Carolina, Charleston, South Carolina, United States
- Staruschenko, Alexander, University of South Florida, Tampa, Florida, United States
Background
Purine catabolism is an essential homeostatic process, with uric acid (UA) serving as its final metabolite in humans. The enzyme xanthine dehydrogenase (XDH) catalyzes the conversion of xanthine to UA. While severe hyperuricemia (HrU) can lead to crystal formation that triggers inflammation and kidney injury, recent studies suggest that renal damage primarily results from UA crystal deposition, not from asymptomatic HrU alone. Dietary salt intake plays a major role in hypertension (HTN) and renal function, and further impacts UA levels in plasma and urine. Previously, we created and characterized a hypouricemic model by knocking out the Xdh gene in Dahl salt-sensitive (SS) rats, leading to renal dysfunction and an upregulated inflammatory transcriptomic signature, highlighting the complex role of UA in the kidney.
Methods
To model mild, asymptomatic HrU, we administered 2% oxonic acid (OA) to high salt-fed Dahl SS rats implanted with blood pressure telemeters. To explore UA's inflammatory mechanisms in SS HTN and renal damage, we used bulk RNA sequencing of kidney cortex tissue, followed by Ingenuity Pathway Analysis. Ongoing studies further characterize immune cell infiltration and activation via flow cytometry and immunohistostaining.
Results
After 3 weeks on the OA/HS diets, rats had increased plasma UA compared to the HS-control group. Surprisingly, the increase in UA was associated with significantly attenuated magnitude of SS HTN and a reno-protective phenotype. Furthermore, transcriptomics data suggested an inhibition in inflammatory responses. Upstream regulator analysis revealed a network of genes connected through IL10RA, an anti-inflammatory pathway receptor (predicted to be activated); and STAT3, RELA, and TNF, as pro-inflammatory factors (predicted to be inhibited). The top canonical pathway predictions also included activation of IL-10 signaling (z score=1.6) and inhibition of cytokine storm signaling (z score=-1.9).
Conclusion
In summary, mild HrU in Dahl SS rats attenuates HTN and kidney injury. Transcriptomic results suggest a shift towards the resolution of inflammation. We propose that these protective effects are mediated by the IL-10/STAT3 axis, which opposes the pro-inflammatory effects of TNF-α signaling.
Funding
- Private Foundation Support