Stimulation of Caveolin-1 Signaling Improves Arteriovenous Fistula Patency

Arteriosclerosis, Thrombosis, and Vascular Biology
Takuya HashimotoAlan Dardik

Abstract

Objective- Arteriovenous fistulae (AVF) are the most common access created for hemodialysis; however, many AVF fail to mature and require repeated intervention, suggesting a need to improve AVF maturation. Eph-B4 (ephrin type-B receptor 4) is the embryonic venous determinant that is functional in adult veins and can regulate AVF maturation. Cav-1 (caveolin-1) is the major scaffolding protein of caveolae-a distinct microdomain that serves as a mechanosensor at the endothelial cell membrane. We hypothesized that Cav-1 function is critical for Eph-B4-mediated AVF maturation. Approach and Results- In a mouse aortocaval fistula model, both Cav-1 mRNA and protein were increased in the AVF compared with control veins. Cav-1 KO (knockout) mice showed increased fistula wall thickening ( P=0.0005) and outward remodeling ( P<0.0001), with increased eNOS (endothelial NO synthase) activity compared with WT (wild type) mice. Ephrin-B2/Fc inhibited AVF outward remodeling in WT mice but not in Cav-1 KO mice and was maintained in Cav-1 RC (Cav-1 endothelial reconstituted) mice (WT, P=0.0001; Cav-1 KO, P=0.7552; Cav-1 RC, P=0.0002). Cavtratin-a Cav-1 scaffolding domain peptide-decreased AVF wall thickness in WT mice and in Eph-B4 het mice compar...Continue Reading

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Citations

Oct 15, 2019·Vascular Investigation and Therapy·Jolanta GoreckaAlan Dardik
Jun 27, 2020·Journal of the American Society of Nephrology : JASN·Chuanqi CaiSanjay Misra
Jan 22, 2021·Arteriosclerosis, Thrombosis, and Vascular Biology·Yutaka Matsubara (松原裕)Alan Dardik
Feb 6, 2021·Journal of Vascular Surgery. Vascular Science·Ryosuke TaniguchiAlan Dardik
Nov 15, 2020·Current Opinion in Cell Biology·Miguel A Del PozoAsier Echarri

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