Are we curing one evil with another? A translational approach targeting the role of neoatherosclerosis in late stent failure

Abstract

Neoatherosclerosis is defined as foamy macrophage infiltration into the peri-strut or neointimal area after stent implantation, potentially leading to late stent failure through progressive atherosclerotic changes including calcification, fibroatheroma, thin-cap fibroatheroma, and rupture with stent thrombosis (ST) in advanced stages. Human autopsy as well as intravascular imaging studies have led to the understanding of neoatherosclerosis formation as a similar but significantly accelerated pathophysiology as compared to native atherosclerosis. This acceleration is mainly based on disrupted endothelial integrity with insufficient barrier function and augmented transmigration of lipids following vascular injury after coronary intervention and especially after implantation of drug-eluting stents. In this review, we summarize translational insights into disease pathophysiology and discuss therapeutic approaches to tackle this novel disease entity. We introduce a novel animal model of neoatherosclerosis alongside accompanying in vitro experiments, which show impaired endothelial integrity causing increased permeability for low-density lipoprotein cholesterol resulting in foam cell transformation of human monocytes. In addition, we discuss novel intravascular imaging surrogates to improve reliable diagnosis of early stage neoatherosclerosis. Finally, a therapeutic approach to prevent in-stent neoatherosclerosis with magnesium-based bioresorbable scaffolds and systemic statin treatment demonstrated the potential to improve arterial healing and re-endothelialization, leading to significantly mitigated neoatherosclerosis formation in an animal model of neoatherosclerosis.

Development and validation of a nomogram for ISR within 2 years in patients after iliac or femoral artery stent placement

“…A meta-analysis showed that the risk of LEASO was higher in patients with familial hypercholesterolemia [19].Excessive cholesterol in the vascular promotes endothelial dysfunction and activates in ammatory cells,which leads to increased production of in ammatory cytokines and reactive oxygen species, increased expression of adhesion molecules,which is an important step in the development of LEASO [20].Hyperlipidemia plays an equally important role in ISR [ 21].In our study, hyperlipidemia was de ned as TG > 1.70mmol / L or TC > 5.72mmol / L or both.Anatomical and intravascular imaging studies have recognized that neoatherosclerosis plays an important role in the occurrence of ISR.Neoatherosclerosis is de ned as foamy macrophage in ltration into the peri-strut or neointimal area after stent implantation, potentially leading to ISR,and hyperlipidemia accelerates this process [22,23].In addition to hyperlipidemia, the below-the-knee run-offs is an independent risk factor affecting the patency of stents [24], which was also veri ed in our study .Initiative management of belowthe-knee run-offs may reduce the incidence of ISR.…”