Relationship between hemodynamics and in-stent restenosis in femoral arteries

Although percutaneous transluminal angioplasty with stenting is one of the preferred treatments of lower extremity peripheral artery disease, this procedure suffers from a 66% 1-year primary patency rate. The unfavorable outcome is mostly attributable to in-stent restenosis, an inflammatory-driven arterial response, characterized by excessive smooth muscle cell proliferative and synthetic activity ultimately leading to lumen re-narrowing. The etiology of in-stent restenosis is multifactorial, involving different systemic, biological and biomechanical drivers. Among the biomechanical factors, a key role has been recognized to the stent-induced hemodynamic alteration, influencing smooth muscle cell activity both directly and through endothelium-dependent mechanisms. In this scenario, computational fluid dynamics simulations of stented femoral arteries allowed quantifying the local hemodynamics and identifying wall shear stress-based hemodynamic predictors of in-stent restenosis. This contributed to enhance the current knowledge of the fluid dynamic-related mechanisms of post-stenting lumen remodeling. However, given the multiscale and multifactorial nature of in-stent restenosis, multiscale mechanobiological modeling relating the intervention-induced mechanical stimuli to the complex network of biological events has recently emerged as a fundamental approach to decipher the underlying pathological pathways. This involves the analysis of interactions, cause-effect relationships, feedback mechanisms and cascade signaling pathways across different spatial and temporal scales, thus allowing tracking the effect of the interventioninduced perturbation to the molecular, cellular and finally tissue response. The present chapter examines the state-of-the-art of computational fluid dynamics studies of in-stent restenosis in femoral arteries and provides an overview on the emerging field of multiscale mechanobiological modeling of arterial adaptation following endovascular procedures.