Familial hypercholesterolaemic downsized pig with human-like coronary atherosclerosis: a model for preclinical studies
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Familial hypercholesterolaemic downsized pig with human-like coronary atherosclerosis: a model for preclinical studies. / Thim, Troels; Hagensen, Mette; Drouet, L.; Bal Dit, Sollier C.; Bonneau, M.; Granada, J.F.; Nielsen, Lars Bo; Paaske, W.P.; Botker, H.E.; Falk, E.
In: EuroIntervention, Vol. 6, No. 2, 2010, p. 261-268.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Familial hypercholesterolaemic downsized pig with human-like coronary atherosclerosis: a model for preclinical studies
AU - Thim, Troels
AU - Hagensen, Mette
AU - Drouet, L.
AU - Bal Dit, Sollier C.
AU - Bonneau, M.
AU - Granada, J.F.
AU - Nielsen, Lars Bo
AU - Paaske, W.P.
AU - Botker, H.E.
AU - Falk, E.
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
M3 - Journal article
VL - 6
SP - 261
EP - 268
JO - EuroIntervention
JF - EuroIntervention
SN - 1774-024X
IS - 2
ER -
ID: 33815258