Cardiovascular stents, fluid flow and endothelial cell phenotype

Coronary heart disease is a major cause of death worldwide, and stenting has become one of the preferred therapies for treatment. In the USA alone about 650,000 stents are implanted yearly with 75% of these being drug eluting stents (DES). Unfortunately 1/3 of patients with bare metal stents (BMS) suffer from restenosis of the coronary artery, and about 1-2% of patients with DES suffer from in-stent thrombosis, leading to significant morbidity and mortality.

Left: Pathlines generated by 1 µm fluorescent particles in the vicinity of 5 different stent strut models under steady flow conditions demonstrate the formation of a range of recirculation zones by different geometries. Right: Representative images of proximal and distal fluorescent fibrin deposition near different stent strut models for pulsatile undisturbed flow inlet boundary condition.

Our research explores how blood flow perturbations caused by the stent design contribute to in-stent restenosis and thrombosis, studying the impact of the fluid forces on blood components and endothelial cells. We have introduced aerodynamic and fluid dynamic engineering principles into stent design, creating streamlined stent struts that differ from commercially available BMS and DES non-streamlined stent struts. Using stented coronary artery models exposed to coronary-like arterial fluid flows we examine: 1) the phenotype change of endothelial cells transcriptionally and/or translationally in the vicinity of nonstreamlined and streamlined stent struts, 2) endothelial cell migration (motility) under the influence of fluid flows created by the different stents struts, with implications to wound healing after coronary artery stenting, a marker of clinical success, 3) in the absence of endothelial cells, the role that stent geometries effect on coagulation and thrombus formation using freshly isolated blood.
Initial results have demonstrated that by introducing this novel engineering approach to stent design, the local blood flow field is changed yielding an anti-thrombotic endothelial cell phenotype and decreased thrombus formation, with implications for clinical success.

Future research planned includes determining the molecular basis for fluid flow-induced differences in endothelial cell migration, optimization of streamlined stent design, and pre-clinical studies of streamlined stents in coronary heart disease animal models.