Abstract: PO1012
Autophagy Response and Arteriovenous Fistula Maturation
Session Information
- Vascular Access Arena: Challenges, Progress, and Prospects
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Dialysis
- 703 Dialysis: Vascular Access
Authors
- Isayeva Waldrop, Tatyana, The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Somarathna, Maheshika Srimali, The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Ingle, Kevin Andrew, The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Lee, Timmy C., The University of Alabama at Birmingham, Birmingham, Alabama, United States
Background
Arteriovenous fistula (AVF) are the preferred vascular access for hemodialysis. AVF creation results in disturbed blood flow within the AVF anastomosis. The objectives of this study were to: 1. Characterize autophagy flux after AVF creation, and during the remodeling process, 2. Use an in vitro model to evaluate autophagy status during the laminar and turbulent flow.
Methods
Femoral AVFs were created in male rats. Yorkshire pigs were used to create carotid artery-jugular vein AVF. Autophagy flux was evaluated after 1 hour and 7 days. AVF and contralateral vessels were harvested for histology and Western blot (WB). Autophagy-related proteins were analyzed in the AVF human vein samples. Effects of hemodynamic changes were investigated by utilizing an in vitro model. Human umbilical vein smooth muscle cells and endothelial cells were co-cultured in the vessel-like system under laminar or disturbed flow conditions. After 24 hours, cells were harvested for histology and WB.
Results
In the rat model impaired autophagy flux was observed in the vein 1 hour after AVF creation. At day 7 expression of ATG3 and ATG7 protein was significantly higher (p<0.003) in the AVF vein compare to contralateral control. Significant increases in p62 expression was detected in 7 days AVF vein (p<0.001) in both in vivo models. Disturbed autophagy flux also observed in human vein samples collected during new AVF creation. In vitro model showed dysregulation of autophagy flux in disturbed flow, as compared to laminar flow.
Conclusion
Our in vitro and in vivo studies both demonstrated that autophagy response may play an important role in vessel remodeling in the setting of disturbed flow as seen in AVFs. Autophagy may be a potential target to improve AVF maturation.
Funding
- NIDDK Support