Atherogenesis in the Carotid Artery with and without Interrupted Blood Flow of Two Hyperlipidemic Mouse Strains

Abstract

Purpose: Atherosclerosis in the carotid arteries is a common cause of ischemic stroke. We examined atherogenesis in the left carotid artery with and without interrupted blood flow of C57BL/6 (B6) and C3H-Apoe-deficient (Apoe^–/–) mouse strains. Methods: Blood flow was interrupted by ligating the common carotid artery near its bifurcation in one group of mice and another group was not interrupted. Results: Without interference with blood flow, C3H-Apoe^–/– mice developed no atherosclerosis in the carotid artery, while B6-Apoe^–/– mice formed advanced atherosclerotic lesions (98,019 ± 10,594 μm²/section) after 12 weeks of a Western diet. When blood flow was interrupted by ligating the common carotid artery near its bifurcation, C3H-Apoe^–/– mice showed fatty streak lesions 2 weeks after ligation, and by 4 weeks fibrous lesions had formed, although they were smaller than in B6-Apoe^–/– mice. Neutrophil adhesion to endothelium and infiltration in lesions was observed in ligated arteries of both strains. Treatment of B6-Apoe^–/– mice with antibody against neutrophils had little effect on lesion size. Conclusions: These findings demonstrate the dramatic influences of genetic backgrounds and blood flow on atherogenesis in the carotid artery of hyperlipidemic mice.