Intramural coronary lipid injection induces atheromatous lesions expressing proinflammatory chemokines: implications for the development of a porcine model of atherosclerosis.

摘要

BACKGROUND: Intramural delivery of lipids into the coronaries of pigs fed high-cholesterol diet results in the formation of localized atherosclerotic-like lesions within 12 weeks. These lesions are located in positively remodeled vessels and are associated to the development of abundant adventitial vasa vasorum and mononuclear cell infiltrate. In this study, we aimed to analyze the degree of expression of various inflammatory chemokines within the developed lesions compared with control segments injected with saline. METHODS: Balloon injury was performed in 15 coronary arteries of pigs fed high-cholesterol diet for 12 weeks. Two weeks after procedure, 60 coronary segments were randomized to either intramural injections of complex lipids (n=30) or normal saline (n=30). Neovessel density in the lesions was analyzed by lectin stain. Segments were processed for RNA expression of inflammatory chemokines such as monocyte chemoattractant protein-1 and vascular endothelial growth factor. RESULTS: At 12 weeks, the percentage area of stenosis seen in histological sections was modest in both groups (lipids: 17.3+/-15 vs. saline: 32.4+/-22.8, P=.017). The lipid group showed higher vasa vasorum (VV) quantity (saline: 18.2+/-14.9 VV/section vs. lipids: 30.6+/-21.6 VV/section, P<.05) and vasa vasorum density (saline: 7.3+/-4.6 VV/mm(2) vs. lipids: 16.5+/-9 VV/mm(2), P<.001). In addition, monocyte chemoattractant protein-1 expression was higher in the lipid group (1.5+/-1.12) compared with saline control group (0.83+/-0.34, P<.01). Vascular endothelial growth factor expression was also higher in the lipid group (1.36+/-0.9) compared with saline group (0.87+/-0.33, P<.05). CONCLUSION: The intramural injection of complex lipids into the coronary arteries of pigs maintained in a high-cholesterol diet results in focal lesions located in positively remodeled vessels that have a high neovessel count and express proinflammatory chemokines.