Low WSS Induces Intimal Thickening, while Large WSS Variation and Inflammation Induce Medial Thinning, in an Animal Model of Atherosclerosis

PLoS One. 2015 Nov 17;10(11):e0141880. doi: 10.1371/journal.pone.0141880. eCollection 2015.


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.

Conclusion: 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.

MeSH terms

  • Animals
  • Atherosclerosis / diagnostic imaging
  • Atherosclerosis / etiology
  • Atherosclerosis / pathology*
  • Biomechanical Phenomena
  • Carotid Arteries / diagnostic imaging
  • Carotid Arteries / pathology
  • Carotid Intima-Media Thickness
  • Endothelium, Vascular / pathology
  • Hypercholesterolemia / complications
  • Phagocytes / pathology
  • Swine
  • Swine, Miniature
  • Vasculitis / metabolism
  • Vasculitis / pathology

Grant support

Two authors (Nicolas Provost and Zouher Majd) are employed by a commercial company: Genfit. Their contributions to this work have been specified. The funder provided support in the form of salaries for authors NP and ZM, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the Author Contributions section.