TY - JOUR
T1 - Are we curing one evil with another? A translational approach targeting the role of neoatherosclerosis in late stent failure
AU - Lenz, Tobias
AU - Nicol, Philipp
AU - Castellanos, Maria Isabel
AU - Abdelgalil, Ayat Aboutaleb Abdellah
AU - Hoppmann, Petra
AU - Kempf, Wolfgang
AU - Koppara, Tobias
AU - Lahmann, Anna Lena
AU - Rüscher, Alena
AU - Kessler, Horst
AU - Joner, Michael
N1 - Publisher Copyright:
© The Author(s) 2020.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - Coronary artery disease
KW - Intravascular imaging
KW - Late stent failure
KW - Magmaris BRS
KW - Neoatherosclerosis
UR - http://www.scopus.com/inward/record.url?scp=85100890087&partnerID=8YFLogxK
U2 - 10.1093/EURHEARTJ/SUAA006
DO - 10.1093/EURHEARTJ/SUAA006
M3 - Article
AN - SCOPUS:85100890087
SN - 1520-765X
VL - 22
SP - C15-C25
JO - European Heart Journal, Supplement
JF - European Heart Journal, Supplement
ER -