Coronary atherosclerotic plaque composition and classification in hypercholesterimic pigs

ABSTRACT 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. 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 size, necrotic core area and fibrous cap thickness. Multifeatured clustering algorithm identified 4 clearly distinguishable plaque groups (A-D). 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, 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. Our results indicate that porcine plaque type A, B, C and D correspond to human type III (intermediate lesion), type IV (atheroma), type V (fibroatheroma) and type VI (high-risk vulnerable plaque), respectively. Overall, 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.