Abstract: SA-PO0434
Spatiotemporal Transcriptomics Analysis of Central Venous Stenosis Suggests Tumor Necrosis Factor (TNF)-α as a Therapeutic Target in Rats with CKD
Session Information
- Dialysis: Vascular Access
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Dialysis
- 803 Dialysis: Vascular Access
Authors
- Lotfollahzadeh, Saran, Boston Medical Center, Boston, Massachusetts, United States
- Malikova, Marina A., Boston Medical Center, Boston, Massachusetts, United States
- Kolachalama, Vijaya B., Boston University, Boston, Massachusetts, United States
- Chitalia, Vipul C., Boston Medical Center, Boston, Massachusetts, United States
Background
In the U.S., 50-80% of CKD patients use a central venous catheter (CVC) for HD. CVC is a strong risk factor for central venous stenosis (CVS), with a prevalence of up to 40%. Little is known about its pathogenesis and treatment, due to a lack of animal models.
Methods
CKD rats were subjected to guide wire injury on their Internal Jugular Veins (IJV). Animals were harvested on days 0, 5, and 14. GeoMx transcriptome analysis and molecular studies were performed.
Results
Injured IJV of CKD rats showed significantly higher thrombus, extracellular matrix, and perivascular fibrosis, consistent with CVS, compared to controls. Spatial transcriptomics analysis revealed several genetic perturbations at different time points in Endothelial Cells (ECs) and VSMCs of CKD rats. Prominent upregulation was noted in the TNF family (Tnfrsf1b, Traf3, ifnb1, Tradd) in ECs and VSMCs at 5 and 14 days post-injury. Rich proximal and distal cross-talks between ECs and VSMCs were noted on days 5 and 14. Immuno Fluorescence assays validated TNF-α upregulation in the ECs of the injured IJVs of CKD compared to control rats(P=0.002). Mechanistic probing revealed that anti-TNF-α neutralizing antibody mitigated uremic serum-induced suppression of ECs survival and improved migration through the JNK/phospho-38 pathway, without a significant effect in primary human VSMCs.
Conclusion
This study demonstrates a CVS model in CKD rats that can be mechanistically probed and therapeutically tested. It also demonstrates the role of TNF-α perturbation in improving ECs' function without effect on VSMCs, ensuring timely EC wound closure to reduce CVS severity.
Ligand-receptor analysis of IJVs normalized to controls showed the ligand-receptor interactions on Days 0, 5, and 14.
Funding
- NIDDK Support