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American Heart Association

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Final ID: We0072

Matrix metalloproteinases-3 promotes arteriovenous fistula failure by regulating FAK-AKT signaling

Abstract Body: Background: Arteriovenous fistulae (AVF) are the preferred surgical procedure for vascular access. However, 60% of AVF fail within one year due to aggressive neointimal hyperplasia, which significantly increases morbidity and mortality. Matrix metalloproteinases-3 (MMP-3), also known as stromelysin-1, is a member of the metalloproteinase family that plays a critical role in the pathogenesis of many human disorders by degrading extracellular matrix and regulating molecular signaling pathways. However, the role of MMP-3 in AVF neointimal failure has not been explored. Methods and Results: We observed that MMP-3 was time-dependently induced by FBS and the growth factor PDGF-BB in cultured venous SMCs. MMP-3 was also highly expressed in the venous neointimal SMCs in an AVF rodent model, as well as in human AVF specimens. Knockdown of MMP-3 significantly suppressed venous SMC proliferation, whereas overexpression of MMP-3 facilitated cell growth in vitro. Importantly, deficiency of global and SMC-specific MMP-3 significantly reduced neointimal hyperplasia and improved patency after AVF creation. Mechanistic studies showed that MMP-3-mediated SMC proliferation and AVF neointimal hyperplasia were regulated via the FAK-AKT signaling pathway. Conclusion: These data suggest that MMP-3 is a key mediator of AVF neointimal failure. Targeting MMP-3 may be a novel therapeutic strategy to prevent AVF neointimal failure and improve overcomes in patients requiring hemodialysis.
  • Xie, Yangzhouyun  ( Yale School of Medicine , New Haven , Connecticut , United States )
  • Cai, Yujun  ( Yale School of Medicine , New Haven , Connecticut , United States )
  • Zhang, Weichang  ( Yale University , New Haven , Connecticut , United States )
  • Thaxton, Carly  ( Yale School of Medicine , New Haven , Connecticut , United States )
  • Jin, Ying  ( Yale School of Medicine , New Haven , Connecticut , United States )
  • Yatsula, Bogdan  ( Yale School of Medicine , New Haven , Connecticut , United States )
  • Davis, Sean  ( Yale University , New Haven , Connecticut , United States )
  • Exsted, Tobias  ( Yale University , New Haven , Connecticut , United States )
  • Dardik, Alan  ( Yale University , New Haven , Connecticut , United States )
  • Guzman, Raul  ( Yale New Haven Hospital , New Haven , Connecticut , United States )
  • Author Disclosures:
    Yangzhouyun Xie: DO NOT have relevant financial relationships | Yujun Cai: DO NOT have relevant financial relationships | Weichang Zhang: No Answer | Carly Thaxton: DO NOT have relevant financial relationships | Ying Jin: No Answer | Bogdan Yatsula: No Answer | Sean Davis: DO NOT have relevant financial relationships | Tobias Exsted: No Answer | Alan Dardik: DO NOT have relevant financial relationships | Raul Guzman: DO NOT have relevant financial relationships
Meeting Info:
Session Info:

08. Poster Session 2 & Reception Sponsored by the ATVB Journal

Wednesday, 04/23/2025 , 05:00PM - 07:00PM

Poster

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