Document Detail


Familial hypercholesterolaemic downsized pig with human-like coronary atherosclerosis: a model for preclinical studies.
MedLine Citation:
PMID:  20562079     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIMS: 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.
METHODS AND RESULTS: 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.
CONCLUSIONS: This human-like porcine model of coronary atherosclerosis is practical and highly relevant for translational research in percutaneous coronary interventions and imaging.
Authors:
Troels Thim; Mette Kallestrup Hagensen; Ludovic Drouet; Claire Bal Dit Sollier; Michel Bonneau; Juan F Granada; Lars Bo Nielsen; William P Paaske; Hans Erik Bøtker; Erling Falk
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology     Volume:  6     ISSN:  1969-6213     ISO Abbreviation:  EuroIntervention     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-06-21     Completed Date:  2010-12-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101251040     Medline TA:  EuroIntervention     Country:  France    
Other Details:
Languages:  eng     Pagination:  261-8     Citation Subset:  IM    
Affiliation:
Atherosclerosis Research Unit, Department of Cardiology, Aarhus University Hospital (Skejby) and Institute of Clinical Medicine, Aarhus University, Denmark. troels.thim@ki.au.dk
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MeSH Terms
Descriptor/Qualifier:
Animals
Body Size
Coronary Artery Disease*
Disease Models, Animal*
Hyperlipoproteinemia Type II*
Male
Swine

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