Vascular stenosis: biology and interventions

Abstract

Vascular access dysfunction remains a significant cause of morbidity and mortality for hemodialysis patients. We believe that a better understanding of the biological mechanisms of vascular access stenosis will help guide the development of novel therapies to prevent and treat dialysis access stenosis.

Induction of Heme Oxygenase-1 is a Beneficial Response in a Murine Model of Venous Thrombosis

“…Failure of these fistulas is often due, as a terminal event, to thrombotic luminal occlusion of the venous limb, the latter thickened and stenosed by neointima hyperplasia and inflammation. 46,47 Thrombosed arteriovenous fistulas exhibit, as compared with nonthrombosed fistulas, marked inflammatory responses in the venous wall, and significantly increased expression of MMP-9, the latter localizing, mainly, to leukocytes present in the subintimal area of the venous wall. 48 It has been suggested that such expression of MMP-9 lyses the extracellular matrix and damages the endothelium such that the latter assumes procoagulant properties that promote thrombosis.…”

Hemodialysis Vascular Access Dysfunction

“…Poor hemodynamic profiles could be a risk factor for neointimal hyperplasia development and poor venous dilatation, and the degree of luminal stenosis is dependent upon both the magnitude of neointimal hyperplasia and the capacity for vasodilatation or vasocontriction. Therefore, a significant amount of neointimal hyperplasia and medial hypertrophy may not result in luminal stenosis in the presence of adequate vasodilatation, while a small amount of neointimal hyperplasia, but with poor vasodilatation, may result in severe venous stenosis 4,124 . Unfortunately, the factors that are responsible for vascular remodeling are unknown, but adventitial angiogenesis and scar formation are hypothesized to play a significant role 125,126 .…”

“…We now understand that the most common pathologic lesion seen in AVF and AVG dysfunction is aggressive venous neointimal hyperplasia, and biofilms and fibrin sheaths play a major role in CVC infection and dysfunction. In order to advance the field further, we need to further our current understanding of both the clinical and experimental pathways that result in venous neointimal hyperplasia and mechanisms that lead to biofilm and fibrin sheath production in C V C s b y u s i n g t h e a d v a n c e d technologies and tools in cellular and molecular biology, bioengineering, genomics, proteomics, and vascular imaging (ultrasound, computed tomography, and magnetic resonance imaging) 65,124,214 . Finally, small and large animal models of AVF and AVG, which a number of investigators in this field have already developed 61,93,207,[215][216][217] , will play an essential role in "translating" our knowledge of pathophysiologic mechanisms in vascular access dysfunction to novel therapies for patients.…”

Characterization of a Model of an Arteriovenous Fistula in the Rat

“…However, AVFs may fail either at a relatively early or a more delayed time point after which they were created. [1][2][3][4][5][6] Early or primary failure of an AVF represents maturational failure of the fistula such that it can never be used for hemodialysis; this early failure may reflect either an intrinsic inability of the vascular segments to dilate and accommodate enhanced blood flow, the presence of juxta-anastomotic stenosis, or the presence of accessory veins. Late or secondary failure of an AVF occurs when a fistula loses its capacity to sustain hemodialysis because of vascular stenosis or thrombosis, or a combination of both processes.…”

“…[1][2][3][4][5][6] Such vascular access dysfunction and its complications commonly contribute to the hospitalization of patients on maintenance hemodialysis, and accrue, on a yearly basis, well over a billion dollars in health care costs.…”