title: Peristrut microhemorrhages: a possible cause of in-stent neoatherosclerosis?
abstract: BACKGROUND
  In-stent neoatherosclerosis is characterized by the delayed appearance of markers of atheroma in the subintima, but the pathophysiology underlying this new disease entity remains unclear.
  
  
  RESULTS
  We collected 20 human coronary artery stents by removal from explanted hearts. The mean duration of stent implantation was 34 months. In all samples, neoatherosclerosis was detected, particularly in peristrut areas. It consisted of foam cells and cholesterol clefts, with or without calcification, associated with neovascularization. Iron and glycophorin-A were present in peristrut areas, as well as autofluorescent ceroids. Moreover, in response to neoatherosclerosis, tertiary lymphoid organs (tissue lymphoid clusters) often developed in the adventitia. Some of these features could be reproduced in an experimental carotid stenting model in rabbits fed a high-cholesterol diet. Foam cells were present in all samples, and peristrut red blood cells (RBCs) were also detected, as shown by iron deposits and Bandeiraea simplicifiola isolectin-B4 staining of RBC membranes. Finally, in silico models were used to evaluate the compliance mismatch between the rigid struts and the distensible arterial wall using finite element analysis. They show that stenting approximately doubles the local von Mises stress in the intimal layer.
  
  
  CONCLUSIONS
  We show here that stent implantation both in human and in rabbit arteries is characterized by local peristrut microhemorrhages and finally by both cholesterol accumulation and oxidation, triggering together in-stent neoatherosclerosis. Our data indicate that these processes are likely initiated by an increased mechanical stress due to the compliance mismatch between the rigid stent and the soft wall.
authors.affiliation: INSERM U1148, Université Paris-Diderot, Sorbonne Paris-Cité, DHU-FIRE, Hôpital Bichat, Paris, France; Departments of Cardiology, Nuclear Medicine, and Cardiac Surgery, Assistance Publique-Hôpitaux de Paris, DHU-FIRE, RHU iVASC, Hôpital Bichat, Paris, France.
authors.forename: Zaven
authors.initials: Z
authors.lastname: Terzian
authors.affiliation: Department of Solid Mechanics, School of Engineering Sciences, KTH Royal Institute of Technology, 100 44, Stockholm, Sweden.
authors.forename: T Christian
authors.initials: TC
authors.lastname: Gasser
authors.affiliation: INSERM U1148, Université Paris-Diderot, Sorbonne Paris-Cité, DHU-FIRE, Hôpital Bichat, Paris, France; Departments of Cardiology, Nuclear Medicine, and Cardiac Surgery, Assistance Publique-Hôpitaux de Paris, DHU-FIRE, RHU iVASC, Hôpital Bichat, Paris, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Blackwell
authors.affiliation: INSERM U1148, Université Paris-Diderot, Sorbonne Paris-Cité, DHU-FIRE, Hôpital Bichat, Paris, France; Departments of Cardiology, Nuclear Medicine, and Cardiac Surgery, Assistance Publique-Hôpitaux de Paris, DHU-FIRE, RHU iVASC, Hôpital Bichat, Paris, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Hyafil
authors.affiliation: INSERM U1148, Université Paris-Diderot, Sorbonne Paris-Cité, DHU-FIRE, Hôpital Bichat, Paris, France.
authors.forename: Liliane
authors.initials: L
authors.lastname: Louedec
authors.affiliation: INSERM U1148, Université Paris-Diderot, Sorbonne Paris-Cité, DHU-FIRE, Hôpital Bichat, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Deschildre
authors.affiliation: Departments of Cardiology, Nuclear Medicine, and Cardiac Surgery, Assistance Publique-Hôpitaux de Paris, DHU-FIRE, RHU iVASC, Hôpital Bichat, Paris, France.
authors.forename: Walid
authors.initials: W
authors.lastname: Ghodbane
authors.affiliation: INSERM U1148, Université Paris-Diderot, Sorbonne Paris-Cité, DHU-FIRE, Hôpital Bichat, Paris, France; Departments of Cardiology, Nuclear Medicine, and Cardiac Surgery, Assistance Publique-Hôpitaux de Paris, DHU-FIRE, RHU iVASC, Hôpital Bichat, Paris, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Dorent
authors.affiliation: INSERM U1148, Université Paris-Diderot, Sorbonne Paris-Cité, DHU-FIRE, Hôpital Bichat, Paris, France.
authors.forename: Antonino
authors.initials: A
authors.lastname: Nicoletti
authors.affiliation: INSERM U1148, Université Paris-Diderot, Sorbonne Paris-Cité, DHU-FIRE, Hôpital Bichat, Paris, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Morvan
authors.affiliation: INSERM U1148, Université Paris-Diderot, Sorbonne Paris-Cité, DHU-FIRE, Hôpital Bichat, Paris, France; Interventional Cardiology, Centre Cardiologique du Nord, Saint-Denis, France.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Nejjari
authors.affiliation: INSERM U1148, Université Paris-Diderot, Sorbonne Paris-Cité, DHU-FIRE, Hôpital Bichat, Paris, France; Departments of Cardiology, Nuclear Medicine, and Cardiac Surgery, Assistance Publique-Hôpitaux de Paris, DHU-FIRE, RHU iVASC, Hôpital Bichat, Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Feldman
authors.affiliation: INSERM U1148, Université Paris-Diderot, Sorbonne Paris-Cité, DHU-FIRE, Hôpital Bichat, Paris, France; Paris13-Nord University-Villetaneuse, Villetaneuse, France.
authors.forename: Graciela
authors.initials: G
authors.lastname: Pavon-Djavid
authors.affiliation: INSERM U1148, Université Paris-Diderot, Sorbonne Paris-Cité, DHU-FIRE, Hôpital Bichat, Paris, France. Electronic address: jean-baptiste.michel@inserm.fr.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Michel
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000473:pathology*; D003324:Coronary Artery Disease / Q000473:pathology* / Q000601:surgery*; D006470:Hemorrhage / Q000473:pathology*; D006801:Humans; D011183:Postoperative Complications / Q000473:pathology*; D011817:Rabbits; D015607:Stents / Q000009:adverse effects*; D013314:Stress, Mechanical
keywords: Cholesterol; Coronary artery disease; Hemoglobin; Hemorrhage; Neoatherosclerosis; Stent