Unraveling the Role of Fibroblast-Derived Lysyl Oxidase in AVF Maturation Failure - Abstract End-stage kidney disease affects over 800,000 Americans, with ~60% undergoing hemodialysis (HD). For these patients on HD, vascular access is critical, with three main types available: central venous catheter, arteriovenous graft, and arteriovenous fistula (AVF). Among these, the AVF is the preferred choice due to its superior longevity and lower risk of infection. However, AVFs face significant challenges, as up to 40% require endovascular or surgical intervention to address stenosis, which impairs their ability to function for dialysis. These frequent interventions increase the risk of complications and hospitalizations, contributing to the high annual cost of maintaining vascular access, which exceeds $2 billion. Thus, there is an urgent need for novel anti-stenotic treatments to enhance AVF maturation and reduce failure rates. In fact, the successful completion of this study will allow me to uncover the role of fibroblast-specific LOX in the maturation and failure of arteriovenous fistulas (AVF). Specifically, I aim to elucidate the molecular and cellular mechanisms by which LOX upregulation increases the risk of AVF failure. Our preliminary data provides a robust foundation to explore LOX's role in modulating fibroblast phenotypes following AVF creation. I am confident that the outcomes of this K01 grant will help identify novel therapeutic targets to prevent or reduce AVF failure in patients with chronic kidney disease (CKD), potentially accelerating the development of innovative treatments. This award will also be instrumental in advancing my career goal of becoming an independent, well-funded scientist and securing a tenure-track faculty position within the Vascular Division of the Department of Surgery at the Miller School of Medicine, University of Miami. My long-term research vision focuses on arterial and venous diseases, with a special emphasis on venous remodeling following surgical interventions such as AVF. Ultimately, my goal is to develop pharmacological and non-pharmacological therapies, including exercise training, to treat arterial and venous disorders and translate these discoveries into clinical practice to improve patient outcomes. By accomplishing the proposed aims and participating in the comprehensive training plan, I will strengthen my expertise in advanced imaging techniques, biostatistics, grant writing, transgenic mouse model management, and genomics. These skills will be critical in my path to scientific independence and will enable me to make significant contributions to the field.
