FH pigs develop complex coronary atheromas that can be classified into 4 distinct groups corresponding to human intermediate to high-risk vulnerable plaques, establishing them as a suitable preclinical model for coronary atherosclerotic disease.
BACKGROUND AND AIMS Rapacz pigs with familial hypercholesterolemia (FH pigs) fed with high-fat diet (HFD) develop early atherosclerotic lesions and complex atheromas in coronaries mimicking human coronary atherosclerotic disease (CAD). FH pigs have proven to be an excellent model for basic and pre-clinical atherosclerosis-focused research. However, unlike human atherosclerosis there has been no established classification system for porcine atherosclerosis. METHODS We isolated 104 plaque-containing coronary fragments from atherosclerotic FH pigs. A set of indices (features) of vessel and plaque morphology were quantified for each plaque, including intima-media ratio, vessel cross-sectional area, necrotic core area and fibrous cap thickness. The unsupervised K-means clustering multi-featured algorithm was used to distinguish coronary plaque groups. Plaque cellular composition was assessed by immunohistochemistry to quantify relative level of smooth muscle-like, endothelial-like and macrophage-like cells. Plaque neovascularization, collagen levels, cell apoptosis, calcification and features of vulnerable plaque were assessed and used as additional numerical criteria for plaque classification and to establish the similarity of porcine plaque to specific types of human lesions. RESULTS The clustering algorithm identified 4 clearly distinguishable plaque groups (A-D). The porcine plaque group A was classified as pre-atheroma and plaque group C-D as advanced atheroma. Our data indicates that porcine plaque group A, B, C and D correspond to human lesions type III (intermediate lesion), type IV (atheroma), type V (fibroatheroma) and type VI (high-risk vulnerable plaque), respectively. CONCLUSIONS Our data demonstrates the suitability of using the FH pig as a pre-clinical model of human-like coronary atherosclerosis with great potential to advance emergent research in the field of CAD, especially in study of vulnerable plaque and in discovery research.
Li et al. (Thu,) studied this question.
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