# Vascular Smooth Muscle Cell Metabolic Reprogramming in Arteriovenous Fistula Failure

## TL;DR

This paper reviews how changes in vascular smooth muscle cell metabolism contribute to the failure of arteriovenous fistulas used in hemodialysis.

## Contribution

The paper provides a comprehensive review of VSMC metabolic reprogramming and its role in AVF failure, highlighting potential therapeutic targets.

## Key findings

- VSMCs undergo metabolic reprogramming due to hyperphosphatemia, uremic toxins, and oxidative stress.
- Metabolic shifts in VSMCs contribute to outward and inward remodeling and medial calcification in AVF failure.
- Therapeutic strategies targeting VSMC metabolism may improve AVF outcomes.

## Abstract

Hemodialysis is the most commonly used renal replacement therapy worldwide, and arteriovenous fistulas (AVFs) are the preferred vascular access. The functional patency of AVFs directly determines the dialysis efficiency and quality of life of patients with end-stage renal disease (ESRD). However, in clinical practice, the failure of AVFs seriously affects the treatment prognosis of these patients. Vascular smooth muscle cells (VSMCs), as the main component of the vascular media, not only maintain the integrity and tension of the vascular wall under physiological conditions but also play a crucial role in the failure of AVF maturation and post-maturation dysfunction. VSMCs undergo metabolic reprogramming along with adaptive structural and functional alterations, driven by persistent stimulation from hyperphosphatemia, uremic toxins, oxidative stress, and inflammatory factors, as well as hemodynamic disturbances induced by AVF creation and surgical trauma. This review summarizes the roles of VSMC metabolic and phenotypic shifts in outward remodeling, inward remodeling, and medial calcification during AVF failure, elaborates on the metabolic crosstalk between VSMCs and endothelial cells, and discusses potential therapeutic targets targeting VSMC metabolism.