Abstract: TH-PO0253
Lysine Attenuates Salt-Sensitive Hypertension via Modifications of Fatty Acid Metabolism
Session Information
- Top Trainee Posters - 1
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 01:24 PM - 01:30 PM
Category: Hypertension and CVD
- 1601 Hypertension and CVD: Basic
Authors
- Dissanayake, Lashodya Vindana, University of South Florida, Tampa, Florida, United States
- Tan, Yifan, Aarhus Universitet, Aarhus, Central Denmark Region , Denmark
- Tiwari, Ratnakar, 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
- Rinschen, Markus M., Aarhus Universitet, Aarhus, Central Denmark Region , Denmark
- Staruschenko, Alexander, University of South Florida, Tampa, Florida, United States
Background
Salt-sensitive (SS) hypertension (HTN) is therapeutically challenging and affects a large proportion of the population. Our previous research shows that supplementing Dahl SS rats with lysine, an essential amino acid, attenuates HTN and kidney damage. The effects were thought to be twofold: 1) facilitating mechanical clearance of tubular proteins via inhibition of proximal reabsorption, and 2) inducing metabolic adaptations in the kidney that confer renoprotection. The current study attempts to clarify specific metabolic adaptations when lysine is administered after HTN has developed.
Methods
We used male Dahl SS rats with radiotelemetry on a high-salt (HS 8% NaCl) diet. When HTN developed (mean arterial pressure (MAP) >140 mmHg), rats were treated with lysine-Cl (17 mg/ml in water) or vehicle. Proteomic analysis was conducted on the kidney, urine, plasma, and liver at the endpoint. Additionally, kidney cortex/medulla at days 0, 7, 14, 21, and 35 of HS (without lysine treatment) were collected and subjected to bulk RNA seq to characterize the changes in pathways of interest in the HTN kidney damage.
Results
Lysine-treated rats exhibited significantly lower MAP (145±4 vs. 179±6 mmHg) and reduced protein cast accumulation in the kidney. Proteomic analysis revealed that the main changes were related to fatty acid (FA) metabolism. Kidney proteome changes suggested acyl-CoA oxidase 1 (ACOX1), the first enzyme necessary for peroxisomal FA oxidation, as an upstream regulator (p-value >4E-03). In the liver, a causal network consisting of master regulators FAF2 and RAS (z-scores 2.3, 2.1) was found to influence changes in FAs. Interestingly, pathway analysis of the medullary transcriptome of HTN rats indicated significant progressive downregulation of lysine catabolism, FA α/β-oxidation, and proxisomal lipid metabolism throughout the time course. Acox1 mRNA showed a continuing decrease, while Pex5, a gene involved in peroxisomal transport, increased during HTN progression.
Conclusion
In summary, lysine supplementation attenuates SS HTN and renal injury, potentially restoring impaired FA metabolism. The protective effect may involve a metabolic shift from mitochondrial to peroxisomal FA oxidation, highlighting a novel therapeutic mechanism in SS HTN.