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Abstract: FR-PO995

Interplay Between Skeletal Muscle Catabolism and Remodeling of Arteriovenous Fistulae via YAP1 Signaling

Session Information

Category: CKD (Non-Dialysis)

  • 2303 CKD (Non-Dialysis): Mechanisms


  • Wu, Yongdong, Baylor College of Medicine, Houston, Texas, United States
  • Liang, Ming, Baylor College of Medicine, Houston, Texas, United States
  • Lee, Tae Hoon, Baylor College of Medicine, Houston, Texas, United States
  • Huang, Fengzhang, Baylor College of Medicine, Houston, Texas, United States
  • Truong, Luan D., Houston Methodist Hospital, Houston, Texas, United States
  • Cheng, Jizhong, Baylor College of Medicine, Houston, Texas, United States

Arteriovenous fistulae (AVFs) are the preferred dialysis access choice, but they are prone to complications and have a high incidence of failure. The aim of this study is to understand the crosstalk of skeletal muscle catabolism and AVF maturation failure, and the role of myostatin and YAP1 signaling pathway in regulating AVF maturation.


AVFs were created in mice with chronic kidney disease (CKD). The skeletal muscle metabolism and AVF maturation were evaluated in mice that were treated with myostatin or its antagonist antibody. The role of YAP1 in transdifferentiation of adventitial mesenchymal stem cells (MSC) into neointima cells was investigated. Finally, “red light”-controlled verteporfin nanoparticles were used to block YAP1 activation in AVFs.


PDGFRA reporter mice showed that positive MSCs were found both in muscle interstitial and vascular adventitial. These MSCs were activated in response to myostatin, that was increased in atrophied muscle fibers in CKD mice and was associated with vascular stiffness. Increased trichrome signals and stenosis were observed in AVFs from mice that were treated with myostatin. In contrast, blocking myostatin function by anti-myostatin peptibody not only improved body weight and muscle size in CKD mice, but also decreased neointima formation in AVFs. These responses were paralleled with decreased accumulation of PDGFRA+ cells in AVFs. In cultured MSCs, YAP1 signaling mediated activation and differentiation of MSCs when MSCs were treated with myostatin or seeded on hard surface. "Red light"-controlled release of verteporfin nanoparticles, YAP1 inhibitor, alleviated MSC activation. Local application of verteporfin nanoparticles significantly suppressed accumulation of neointima cells in AVFs in irradiation group vs non-irradiated groups.


There were increased muscle atrophy and myostatin production in CKD mice, the latter stimulates MSCs activation and vascular fibrosis that are linked to AVF stenosis. YAP1 signaling was activated in this process. Blocking myostatin or inhibiting YAP1 activation suppressed neointimal formation with improved AVF function.


  • NIDDK Support