title: Low WSS Induces Intimal Thickening, while Large WSS Variation and Inflammation Induce Medial Thinning, in an Animal Model of Atherosclerosis.
abstract: OBJECTIVE
  Atherosclerotic plaque development in the arterial wall is the result of complex interaction between the wall's endothelial layer and blood hemodynamics. However, the interaction between hemodynamic parameters and inflammation in plaque evolution is not yet fully understood. The aim of the present study was to investigate the relation between wall shear stress (WSS) and vessel wall inflammation during atherosclerotic plaque development in a minipig model of carotid stenosis.
  
  
  METHODS
  A surgical procedure was performed to create left common carotid artery stenosis by placement of a perivascular cuff in minipigs under atherogenic diet. Animals were followed up on 3T MRI, 1 week after surgery and 3, 6, and 8 months after initiation of the diet. Computational fluid dynamics simulation estimated WSS distribution for the first imaging point. Vascular geometries were co-registered for direct comparison of plaque development and features (Gadolinium- and USPIO-Contrast Enhanced MRI, for permeability and inflammation respectively) with the initial WSS. Histological analysis was performed and sections were matched to MR images, based on spatial landmarks.
  
  
  RESULTS
  Vessel wall thickening, permeability and inflammation were observed distally from the stenosis. They were eccentric and facing regions of normal wall thickness. Histological analysis confirmed eccentric plaque formation with lipid infiltration, intimal thickening and medial degradation. High phagocytic activity in the stenosis region was co-localized with high WSS, corresponding to intense medial degradation observed on histology samples.
  
  
  CONCLUSIONS
  Lower WSS promotes atherosclerotic plaque development distal to an induced stenosis. Vascular and perivascular inflammation locations were predominant in the high WSS stenosis segment, where medial thinning was the major consequence.
authors.affiliation: Lyon-1 University, CREATIS Laboratory, Lyon, France.|Hospices Civils de Lyon, Lyon, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Millon
authors.affiliation: Lyon-1 University, CREATIS Laboratory, Lyon, France.
authors.forename: Monica
authors.initials: M
authors.lastname: Sigovan
authors.affiliation: Lyon-1 University, CREATIS Laboratory, Lyon, France.|Hospices Civils de Lyon, Lyon, France.
authors.forename: Loic
authors.initials: L
authors.lastname: Boussel
authors.affiliation: Hospices Civils de Lyon, Lyon, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mathevet
authors.affiliation: Lyon-1 University, VetAgro Sup, Lyon, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Louzier
authors.affiliation: Lyon-1 University, VetAgro Sup, Lyon, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Paquet
authors.affiliation: Lyon-1 University, CARMEN Laboratory, INSERM U1060, Lyon, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Geloen
authors.affiliation: Genfit Research, Lille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Provost
authors.affiliation: Genfit Research, Lille, France.
authors.forename: Zouher
authors.initials: Z
authors.lastname: Majd
authors.affiliation: Lyon-1 University, CARMEN Laboratory, INSERM U1060, Lyon, France.
authors.forename: David
authors.initials: D
authors.lastname: Patsouris
authors.affiliation: Hospices Civils de Lyon, Lyon, France.
authors.forename: Andre
authors.initials: A
authors.lastname: Serusclat
authors.affiliation: Lyon-1 University, CARMEN Laboratory, INSERM U1060, Lyon, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Canet-Soulas
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology*; D001696:Biomechanical Phenomena; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000473:pathology; D059168:Carotid Intima-Media Thickness; D004730:Endothelium, Vascular / Q000473:pathology; D006937:Hypercholesterolemia / Q000150:complications; D010586:Phagocytes / Q000473:pathology; D013552:Swine; D013556:Swine, Miniature; D014657:Vasculitis / Q000378:metabolism / Q000473:pathology