Role of Endothelial Shear Stress in Stent Restenosis and Thrombosis

Abstract

Restenosis and thrombosis are potentially fatal complications of coronary stenting with a recognized multifactorial etiology. The effect of documented risk factors, however, cannot explain the preponderance of certain lesion types, stent designs, and implantation configurations for the development of these complications. Local hemodynamic factors, low endothelial shear stress (ESS) in particular, are long known to critically affect the natural history of atherosclerosis. Increasing evidence now suggests that ESS may also contribute to the development of restenosis and thrombosis upon stenting of atherosclerotic plaques, in conjunction with well-appreciated risk factors. In this review, we present in vivo and mechanistic evidence associating ESS with the localization and progression of neointimal hyperplasia and in-stent clotting. Clinical studies have associated stent design features with the risk of restenosis. Importantly, computational simulations extend these observations by directly linking specific stent geometry and positioning characteristics with the post-stenting hemodynamic milieu and with the stent's thrombogenicity and pro-restenotic potential, thereby indicating ways to clinical translation. An enhanced understanding of the pathophysiologic role of ESS in restenosis and thrombosis might dictate hemodynamically favorable stent designs and deployment configurations to reduce the potential for late lumen loss and thrombotic obstruction. Recent methodologies for in vivo ESS profiling at a clinical level might allow for early identification of patients at high risk for the development of restenosis or thrombosis and might thereby guide individualized, risk-tailored treatment strategies to prevent devastating complications of endovascular interventions.

Mechanisms of Very Late Drug-Eluting Stent Thrombosis Assessed by Optical Coherence Tomography

“…This finding suggests that the likelihood of thrombosis could be greater for any given number of malapposed struts compared with a segment with a similar number of uncovered struts. This is pathomechanistically plausible because malapposed struts are more exposed to disturbed blood flow 26 and are more likely to be associated with underlying vessel inflammation (in case of late acquired malapposition). Our exploratory analysis according to DES type and implantation-to-thrombosis interval provides novel in vivo insights by demonstrating that even >6 years after implantation of paclitaxel-or sirolimuseluting stents, uncovered struts were still associated with the occurrence of stent thrombosis.…”

Shear Stress and Atherosclerosis

“…ECs in these regions have an activated, pro-inflammatory phenotype that is characterized by poor alignment, high turnover, and being under oxidative stress (Ando and Yamamoto, 2009). Furthermore, substantial evidence supports that disturbed flow alters the profile of secreted factors and EC surface molecule expression to that favoring the development of atherosclerosis (Heo et al, 2011b; 2013; Traub and Berk, 1998), thrombosis (Koskinas et al, 2012), and EC dysfunction (Le et al, 2013), supporting that disturbed flow is athero-prone. Again, accumulating evidence suggest that steady laminar flow and disturbed flow have different effects in regulating EC function and subsequent atherosclerotic plaque formation, but lack of knowledge on the molecular mechanisms to define these two different flows effects has hindered our capability of developing anti-atheosclerotic therapy by modulating EC function.…”

Flexibility Test of the Tools of Angioplasty

“…Low endothelial shear stress can affect the emergence of atherosclerosis and restenosis. Stent design, strut thickness and so flexibility have a main role in this field [5].…”