**3.3 Hemodynamic and vascular remodeling in hemodialysis access dysfunction**

A number of experimental studies have shown that turbulent, low flow, low fluid sheer stress are involved in neointimal hyperplasia development 115-119. High sheer stress has been associated with vascular dilatation through inhibition of smooth muscle cell proliferation and high levels of nitric oxide release, whereas low sheer stress has been associated with smooth muscle cell proliferation and lack of vasodilatation 120-123. 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 role125,126. Thus, the ideal therapy for vascular stenosis would be an intervention that would prevent vascular constriction (adverse remodeling) and neointimal hyperplasia4
