The Vasa Vasorum Is the Gateway to Vascular Inflammation Determining Arteriovenous Fistula Outcomes
- Dialysis: Vascular Access
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
- 803 Dialysis: Vascular Access
- Martinez, Laisel, University of Miami School of Medicine, Miami, Florida, United States
- Rojas, Miguel G., University of Miami School of Medicine, Miami, Florida, United States
- Zigmond, Zachary M., Veterans Affairs Medical Center, Miami, Florida, United States
- Pereira-Simon, Simone, University of Miami School of Medicine, Miami, Florida, United States
- Tabbara, Marwan, University of Miami School of Medicine, Miami, Florida, United States
- Vazquez-Padron, Roberto I., University of Miami School of Medicine, Miami, Florida, United States
Postoperative vascular inflammation is believed to contribute to arteriovenous fistula (AVF) maturation failure. However, the cellular mechanisms controlling inflammatory cell recruitment and inflammation resolution after anastomosis remain obscure.
In this work, we used for the first time a combination of single-cell RNA sequencing (scRNAseq) and histologic validations to reveal the place of entrance of inflammatory cells into the venous wall following AVF creation.
Analyses of vascular tissues collected in the first week after AVF creation demonstrate an extensive infiltration of leukocytes in the media and adventitia and less so in the intima. Interestingly, these AVF showed a notable expansion of vasa vasorum (VV) number and size. Next, we characterized the cellular composition of cells forming the VV of pre-access veins and AVF using scRNAseq and validated our findings by immunofluorescence. Single-cell profiling of endothelial cells (ECs) identified markers for arterioles, capillaries, and venules. Immunofluorescence staining demonstrated an abundance of capillaries throughout the entire wall, venules in the outer media and adventitia, and a comparatively smaller number of arterioles in the outer adventitia. Venular ECs had significant upregulation of adhesion molecules with respect to the other endothelial subsets, indicating that they may act as docking sites for leukocyte infiltration. This work demonstrates a diversity of VV in the walls of veins and constitutes an important foundation for the study of intramural vascularization in vascular access remodeling.
In conclusion, our data strongly support the importance of the VV network, and particularly venules, in postoperative inflammation and AVF outcomes. These results also support the perivascular delivery of drugs targeting neoangiogenesis and microvessel permeability as future treatments to improve vascular access outcomes.
- NIDDK Support