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Abstract: SA-OR022

Vascular Remodeling in Human Arteriovenous Fistula Maturation: Roles of β-Catenin, Notch, and Transforming Growth Factor (TGF)-β Signaling Pathways

Session Information

Category: Dialysis

  • 803 Dialysis: Vascular Access

Authors

  • Liu, Chung-te, Taipei Medical University, Taipei City, Taiwan
  • Shiu, Yan-Ting Elizabeth, University of Utah Hospital, Salt Lake City, Utah, United States
Background

The actual effects of various signaling pathways on arteriovenous fistula (AVF) maturation have not been thoroughly examined in human AVF. The present study aims to analyze the histological changes and the status of various signaling pathways in human specimens of native veins and AVFs.

Methods

The present prospective observational study collected 100 native vein specimens from patients receiving AVF creation and check maturation at 3 months. In addition, 6 nonmature AVF and 6 mature AVF from patients receiving surgical revision or repairment of dysfunctional AVF. Whole vessel collagen intensity, smooth muscle intensity, intima and subintima area, and media area were compared between pre-operative veins that remained nonmature and those that matured within three months. Additionally, these parameters were analyzed in nonmature and mature AVFs. The correlation between these parameters and the activation of β-catenin, Notch, and TGF-β signaling pathways were analyzed.

Results

We found that increased vascular collagen intensity may be associated with AVF nonmaturation. Vascular remodeling in AVF appears to involve a reduction in collagen and smooth muscle intensity, alongside an increased intima and subintima areas. (Figure 1) Notch signaling activation is linked to AVF nonmaturation and is significantly correlated with reduced smooth muscle intensity and diminished media area—key factors in AVF nonmaturation during remodeling. In contrast, the suppression of TGF-β signaling is associated with AVF maturation, as it strongly correlates with increased smooth muscle intensity and a reduction in intima and subintima areas. (Figure 2)

Conclusion

Decreased collagen intensity plays a key role in AVF maturation, while high baseline collagen intensity may hinder this process. Suppressed TGF-β signaling supports AVF maturation, whereas Notch signaling activation is linked to non-maturation.

Funding

  • Government Support – Non-U.S.

Digital Object Identifier (DOI)