Coronary atherosclerotic plaque composition and classification in hypercholesterimic pigs.

Area of Science:

• Cardiovascular Research
• Animal Models of Disease
• Atherosclerosis Pathogenesis

Background:

• Familial hypercholesterolemia (FH) pigs on a high-fat diet (HFD) develop coronary atherosclerotic lesions mimicking human coronary atherosclerotic disease (CAD).
• A standardized classification system for porcine atherosclerosis is currently lacking, hindering comparative research.
• FH pigs offer a valuable pre-clinical model for atherosclerosis research.

Purpose of the Study:

• To develop and validate a classification system for coronary atherosclerosis in FH pigs.
• To establish correlations between porcine plaque morphology and human CAD lesion types.
• To underscore the utility of FH pigs as a pre-clinical model for CAD research.

Main Methods:

• Isolation and morphological analysis of 104 coronary plaque fragments from atherosclerotic FH pigs.
• Quantification of plaque features including intima-media ratio, necrotic core area, and fibrous cap thickness.
• Multifeatured clustering, immunohistochemistry, and assessment of neovascularization, collagen, calcification, and vulnerable plaque features.

Main Results:

• A multifeatured clustering algorithm identified four distinct porcine plaque groups (A-D).
• Porcine plaque types A, B, C, and D were found to correspond to human lesion types III, IV, V, and VI, respectively.
• FH pigs exhibit a spectrum of coronary atherosclerosis comparable to human CAD, including vulnerable plaque features.

Conclusions:

• The FH pig model demonstrates significant potential for advancing coronary atherosclerotic disease (CAD) research.
• A validated classification system enhances the utility of FH pigs for studying atherosclerosis, particularly vulnerable plaques.
• This research provides a framework for utilizing FH pigs in pre-clinical discovery research for CAD.