title: Familial hypercholesterolaemic downsized pig with human-like coronary atherosclerosis: a model for preclinical studies.
abstract: A manageable and reproducible large animal model of human-like coronary atherosclerosis is lacking but highly needed for translational research in percutaneous coronary interventions and imaging. Farm pigs with familial hypercholesterolaemia develop advanced atherosclerosis in two to three years but then weigh >200 kg making them impractical and costly. We aimed at down-sizing this pig and accelerating coronary plaque development to make the model more useful and affordable.
  
  
  
  Familial hypercholesterolaemic farm pigs were downsized by crossing them with smaller pigs while preserving their hypercholesterolaemic trait ascribed to a mutation in the low density lipoprotein receptor. We accelerated coronary plaque development by atherogenic diet feeding whereby plasma total cholesterol rose to >20 mmol/l (>800 mg/dl). We further accelerated coronary plaque development site-specifically by inflicting coronary artery balloon injury. Both spontaneously developed and balloon accelerated coronary plaques mirrored pertinent human plaque features, including a large necrotic core covered by a thin and inflamed fibrous cap as seen in the most common type of thrombosis-prone (vulnerable) plaque in humans. Associated vulnerable plaque features included neovascularisation, intraplaque haemorrhage, and expansive remodelling.
  
  
  
  This human-like porcine model of coronary atherosclerosis is practical and highly relevant for translational research in percutaneous coronary interventions and imaging.
authors.affiliation: Atherosclerosis Research Unit, Department of Cardiology, Aarhus University Hospital (Skejby) and Institute of Clinical Medicine, Aarhus University, Denmark. troels.thim@ki.au.dk
authors.forename: Troels
authors.initials: T
authors.lastname: Thim
authors.forename: Mette Kallestrup
authors.initials: MK
authors.lastname: Hagensen
authors.forename: Ludovic
authors.initials: L
authors.lastname: Drouet
authors.forename: Claire
authors.initials: C
authors.lastname: Bal Dit Sollier
authors.forename: Michel
authors.initials: M
authors.lastname: Bonneau
authors.forename: Juan F
authors.initials: JF
authors.lastname: Granada
authors.forename: Lars Bo
authors.initials: LB
authors.lastname: Nielsen
authors.forename: William P
authors.initials: WP
authors.lastname: Paaske
authors.forename: Hans Erik
authors.initials: HE
authors.lastname: Bøtker
authors.forename: Erling
authors.initials: E
authors.lastname: Falk
mesh_terms: D000818:Animals; D049628:Body Size; D003324:Coronary Artery Disease; D004195:Disease Models, Animal; D006938:Hyperlipoproteinemia Type II; D008297:Male; D013552:Swine