Contribution of mechanical and fluid response to in-stent restenosis

Despite the improved success rates of stent implantation for revascularisation of an occlusive atherosclerotic lesion, acute inflammation of the vessel wall and resultant in-stent restenosis still prevail in 10% of all bare metal stent cases. The formation of neointimal hyperplasia (NIH) within the stented region has been suggested to be linked to both the solid mechanics of the vascular wall and the modification of the fluid dynamic environment within the vessel post-stenting. Thus, consideration of both components within stented vessels may provide insights into the processes of initiation and progression of NIH. The pathogenesis of in-stent restenosis (ISR) has been recognised as a wound healing response and arises from four identified phases: thrombosis, inflammation, proliferation, and remodeling. Following the partial denudation of the endothelial cells lining the arterial wall, and exposure of the underlying tissue to intralumenal haemodynamic forces, such as low wall shear stress values (<0.5 Pa), and promotion of shear induced inflammatory cell aggregation, further intimal thickening may result. In addition, the sustained compression on the medial tissue layer following stent deployment may result in local injury of the extracellular matrix and cell death, promoting smooth muscle cell modulation and proliferation.