Building a Scaffold for Arteriovenous Fistula Maturation: Unravelling the Role of the Extracellular Matrix

Abstract

Vascular access is the lifeline for patients receiving haemodialysis as kidney replacement therapy. As a surgically created arteriovenous fistula (AVF) provides a high-flow conduit suitable for cannulation, it remains the vascular access of choice. In order to use an AVF successfully, the luminal diameter and the vessel wall of the venous outflow tract have to increase. This process is referred to as AVF maturation. AVF non-maturation is an important limitation of AVFs that contributes to their poor primary patency rates. To date, there is no clear overview of the overall role of the extracellular matrix (ECM) in AVF maturation. The ECM is essential for vascular functioning, as it provides structural and mechanical strength and communicates with vascular cells to regulate their differentiation and proliferation. Thus, the ECM is involved in multiple processes that regulate AVF maturation, and it is essential to study its anatomy and vascular response to AVF surgery to define therapeutic targets to improve AVF maturation. In this review, we discuss the composition of both the arterial and venous ECM and its incorporation in the three vessel layers: the tunica intima, media, and adventitia. Furthermore, we examine the effect of chronic kidney failure on the vasculature, the timing of ECM remodelling post-AVF surgery, and current ECM interventions to improve AVF maturation. Lastly, the suitability of ECM interventions as a therapeutic target for AVF maturation will be discussed.

Efficacy of cilostazol in promoting the maturation of newly created arteriovenous fistula in patients with end-stage renal disease: a systematic review and meta-analysis

“…32,33 Due to this complex process, the venous outflow tract or the area near the AVF connection (juxta-anastomotic region) is often responsible for AVF maturation and luminal stenosis, possibly due to thrombosis and the development of intimal hyperplasia in the AVF venous outflow tract. 34,35 Thrombosis plays a minor role in the failure of fistula maturation, and intimal hyperplasia is a more significant mechanism. 36,37 Intimal hyperplasia is an inflammatory process triggered by injury that leads to thickening of the intimal layer, proliferation of vascular smooth muscle cells (VSMCs), and deposition of extracellular matrix.…”

Increased expression of the P2Y 12 receptor is involved in the failure of autogenous arteriovenous fistula caused by stenosis

“…[ 66 ] demonstrated that postoperative venous fibrosis increases universally in patients, and only postoperative venous medial fibrosis determines the stenotic potential of intimal hyperplasia in AVF, ultimately establishing vascular fibrosis as a hallmark of AVF failure. TGF-β assumes a central role in kidney and vascular fibrosis and stands as a determinant for AVF functioning [ 67 ]. Additionally, TGF-β orchestrates inflammation within the remodeling AVF wall [ 42 ].…”

Photochemical Modification of the Extracellular Matrix to Alter the Vascular Remodeling Process

“…The successful maturation of a fistula, known as arterialization, hinges on a carefully orchestrated tissue adaptive response, which leads to outward remodeling [7]. The quality and arrangement of the ECM, which governs cellular responses that drive outward-directed proliferation, ensure the requisite thickening of the vein wall without compromising the patency of the venous lumen [8][9][10].…”

“…The significance of the ECM's quality and integrity in regulating vascular remodeling processes is gaining increasing attention as our understanding of its role in governing vascular adaptation responses expands [4,10]. Substantial efforts have been invested in developing engineered ECM scaffolds that mimic the natural mechanical and biological characteristics of the ECM [11].…”