Abstract: SA-OR027
Transcriptional Dynamics in the Swine Arteriovenous Fistula: Bridging Translational Research and Molecular Biology
Session Information
- Dialysis Vascular Access: From Basic Discovery to Translational Science
November 08, 2025 | Location: Room 342D, Convention Center
Abstract Time: 05:50 PM - 06:00 PM
Category: Dialysis
- 803 Dialysis: Vascular Access
Authors
- Martinez, Laisel, University of Miami, Miami, Florida, United States
- Tabbara, Marwan, University of Miami, Miami, Florida, United States
- Pereira-Simon, Simone, University of Miami, Miami, Florida, United States
- Stoyell-Conti, Filipe F., University of Miami, Miami, Florida, United States
- Vazquez-Padron, Roberto I., University of Miami, Miami, Florida, United States
Background
The arteriovenous fistula (AVF) success depends on the coordinated remodeling of arterial and venous limbs. Arterial maladaptation leads to focal stenosis or steal syndrome, while improper venous remodeling results in occlusive stenosis or pseudoaneurysms. This study investigates the convergence and divergence of arterial and venous remodeling following AVF creation to inform vessel-specific therapeutic strategies.
Methods
We established bilateral femoro-femoral AVFs in male and female Yorkshire pigs (n=6). Inflow arteries and outflow veins were analyzed at days 2 and 21 post-anastomosis (n=2 pigs [4 AVFs] per timepoint) using histology and single-cell RNA sequencing. Native arteries and veins from sham-operated pigs (n=2) served as controls.
Results
All AVFs remained patent at day 21, with flows increasing from 523.6 ± 96.5 mL/min at day 2 to 1185.0 ± 170.6 mL/min at day 21. Histology revealed minimal neointima formation at 2 days, and minimal to moderate at 21 days. Integration of 142,052 single cells identified fibroblasts (35 ± 18%), myofibroblasts (15 ± 6%), and monocytes/macrophages (11 ± 5%) as the most abundant populations. Cell proliferation was greater in arteries than in veins. Smooth muscle cells (SMCs) were more prevalent in arteries, while endothelial cells (ECs) and pericytes were enriched in veins due to the expanded vasa vasorum. Immune cell infiltration was more pronounced in veins at day 2, driven by selective recruitment of T cells, NK cells, and dendritic cells. Macrophages and neutrophils in veins exhibited higher inflammatory gene expression than their arterial counterparts. Notably, the unique populations of arterial and venous ECs at baseline experienced a convergence in transcriptional phenotypes over time. Similarly, at day 21, myofibroblasts from both types of vessels showed upregulation of mechanosensitive genes (e.g., THBS4, ACAN, PIEZO2). Cell–cell communication analyses revealed that venous fibroblasts, myofibroblasts, and pericytes were more effective senders of signals to immune cells than their arterial counterparts.
Conclusion
The swine AVF model reveals reciprocal adaptation of the arterial and venous endothelium, accompanied by divergent immune and fibroblast responses, highlighting the need for vascular bed-specific therapeutic strategies.
Funding
- NIDDK Support