The role of cellular senescence in endothelial dysfunction and vascular remodelling in arteriovenous fistula maturation

Haemodialysis (HD) is often required for patients with end-stage renal disease. Arteriovenous fistulas (AVFs), a surgical procedure connecting an artery to a vein, are the preferred vascular access for HD due to their durability and lower complication rates. The aim of AVFs is to promote vein remodelling to accommodate increased blood flow needed for dialysis. However, many AVFs fail to mature properly, making them unsuitable for dialysis. Successful maturation requires remodelling, resulting in an increased luminal diameter and thickened walls to support the increased blood flow. After AVF creation, haemodynamic changes due to increased blood flow on the venous side of the AVF initiate a cascade of events that, when successful, lead to the proper maturation of the AVF, making it suitable for cannulation. In this process, endothelial cells play a crucial role since they are in direct contact with the frictional forces exerted by the blood, known as shear stress. Patients requiring HD often have other conditions that increase the burden of senescent cells, such as ageing, diabetes and hypertension. These senescent cells are characterized by irreversible growth arrest and the secretion of pro-inflammatory and pro-thrombotic factors, collectively known as the senescence-associated secretory phenotype (SASP). This accumulation can impair vascular function by promoting inflammation, reducing vasodilatation, and increasing thrombosis risk, thus hindering proper AVF maturation and function. This review explores the contribution of senescent endothelial cells to AVF maturation and explores potential therapeutic strategies to alleviate the effects of senescent cell accumulation, aiming to improve AVF maturation rates.