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Abstract: FR-PO487

Deficient Endothelial Autophagy Promotes Accelerated Atherosclerosis and Impaired Arteriovenous Fistula (AVF) Remodeling

Session Information

  • Dialysis: Vascular Access
    November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Dialysis

  • 803 Dialysis: Vascular Access

Authors

  • Collie, Paul C., The University of Alabama at Birmingham Department of Medicine, Birmingham, Alabama, United States
  • Ingle, Kevin Andrew, The University of Alabama at Birmingham Department of Medicine, Birmingham, Alabama, United States
  • Isayeva Waldrop, Tatyana, The University of Alabama at Birmingham Department of Medicine, Birmingham, Alabama, United States
  • Gard, William A., The University of Alabama at Birmingham Department of Medicine, Birmingham, Alabama, United States
  • Kim, Jeonga, The University of Alabama at Birmingham Department of Medicine, Birmingham, Alabama, United States
  • Lee, Timmy C., The University of Alabama at Birmingham Department of Medicine, Birmingham, Alabama, United States
Background

Arteriovenous fistulas (AVFs) are the preferred vascular access for hemodialysis patients. Atherosclerosis is highly prevalent in arteries of patients with Chronic Kidney Disease undergoing hemodialysis. We investigated the role of macroautophagy in the venous region of the AVF in an atherosclerotic mouse model.

Methods

At 8-12 weeks of age endothelial cell autophagy-related 7 gene knockout mice with LDLR gene deletion (ecAtg7-/-/LDLR-/-) and mice where the LDLR gene was deleted (LDLR-/-) were introduced to a high fat diet for 3 months before AVF creation surgery. Subsequently, mice underwent AVF surgery using the carotid artery and jugular vein. At day 7 blood flow in the AVF vessels was measured and mice were sacrificed, and histology and oil red staining were performed.

Results

Intimal hyperplasia was significantly greater in the AVF vein in ecAtg7-/-/LDLR-/- mice compared to LDLR-/- mice (p<0.04). Collagen deposition was significantly greater in the AVF arteries and veins in the ecAtg7-/-/LDLR-/- mice compared to LDLR-/- mice (p<0.01).
Oil red staining in the AVF was significantly greater in ecAtg7-/-/LDLR-/- mice compared to LDLR-/- mice (p<0.01). There was a trend towards increased blood flow in AVF vein and arteries in LDLR-/- mice compared to AVF vessels in ecAtg7-/-/LDLR-/-.

Conclusion

Autophagy may play an important role in AVF maturation by worsening atherosclerosis and arterial remodeling, which subsequently impacts vein remodeling.

Funding

  • NIDDK Support