Exosomes in arteriovenous fistula stenosis

Abstract

Arteriovenous fistula (AVF) stenosis is a complex pathological process caused by venous intimal hyperplasia, and its development is influenced by factors such as surgical injury, hemodynamic changes, inflammatory responses, and cellular proliferation and migration. Exosomes are critical mediators of intercellular communication and carry biomolecules (e.g., deoxyribonucleic acid, ribonucleic acid [RNA], and proteins) that can regulate cell functions and impact inflammatory responses, endothelial cell proliferation, and vascular smooth muscle cell migration. Studies have shown that molecules such as microRNAs within exosomes play significant roles in vascular stenosis-related diseases and can function as potential therapeutic tools and biomarkers for disease diagnosis. In addition, exosomes can serve as drug carriers with good biocompatibility and targeting capabilities, providing new avenues for the diagnosis and treatment of AVF stenosis. This article reviews the application of exosomes in AVF stenosis.

Keywords: arteriovenous fistula (AVF); chronic kidney disease (CKD); endothelial-to-mesenchymal transition (EndoMT); exosomes; extracellular vesicles; intimal hyperplasia; vascular remodeling.

FIGURE 1

The biogenesis, release, and interactions with target cells of exosomes. 1. Early endosomes are formed through endocytosis. 2. These develop into multivesicular bodies (MVBs), regulated by ESCRT and tetraspanins. 3. MVBs fuse with lysosomes or the plasma membrane, releasing exosomes. 4. Exosomes interact with recipient cells via endocytosis, receptor-ligand interaction, or fusion Created in BioRender.com.

FIGURE 2

Exosomes are enriched with transmembrane proteins (CD9, CD63), MHC class I/II, TSG101/ALIX (ESCRT), HSP70/90, and various lipids (ceramide, sphingomyelin). Their cargo includes proteins, RNA species, DNA, and metabolites Created in BioRender.com.

FIGURE 3

Isolation and extraction of exosomes. Centrigugal speeds of 300*g, 2000*g, and 10,000*g are used to remove impurities and debris. Exosomes are finally obtained by 100,000*g speed Created in BioRender.com.

FIGURE 4

The process of Intimal Hyperplasia. The process begins with tissue damage and turbulent blood flow, which can injure the endothelial cells lining the blood vessel. Following endothelial injury, platelets and neutrophils aggregate at the site of damage. Then the aggregation of immune cells, such as monocytes and macrophages, leads to the release of pro-inflammatory cytokines like IL-6, IL-8, TNF-α, and reactive oxygen species (ROS) exacerbating the inflammatory response. Under the influence of inflammatory signals, VSMCs undergo a phenotypic switch from a contractile type to a synthetic type Created in BioRender.com.

FIGURE 5

Schematic overview of ferroptosis-related mechanisms regulated by exosomal miRNAs. Ferroptosis is characterized by iron accumulation, lipid peroxidation, and impaired antioxidant defense, particularly through downregulation of GPX4 and system Xc⁻ (SLC7A11). Exosomal miRNAs, such as miR-27a-3p and miR-125b, modulate these pathways by targeting key regulators like SLC7A11, Keap1/Nrf2, or GPX4, thereby influencing ferroptotic sensitivity in vascular cells. Created in BioRender.com.

FIGURE 6

Schematic illustration of exosome-based diagnostic and therapeutic strategies in AVF stenosis. Created in BioRender.com.