Increased atherosclerosis in rabbits immunized with endothelial cells

Abstract

Rabbits maintained on normal ration or cholesterol-supplemented diet were immunized with homogenates of endothelial cells grown in cultures that were derived from either bovine or human aorta. Minimal aortic lesions were found in all groups of rabbits fed regular diet; microscopically, differences were seen that manifested as medial lesions in controls and intimal lesions in animals immunized with endothelial cells. Aortic atherosclerosis was significantly increased in the immunized, cholesterol-fed animals over that in controls. This difference was more pronounced in the abdominal aorta where the area with lesions in immunized rabbits was 4–7 times that of controls; atherosclerosis of the thoracic aorta was 2.5–5 times greater in the immunized animals ( P < 0.001 for both segments). Increased atherosclerosis was observed despite a significant reduction in plasma cholesterol in the immunized rabbits (770 ± 119 mg/dl) compared to controls (1595 ± 225 mg/dl) ( P < 0.001). Immunization with endothelial cells elicited strong cell-mediated and humoral responses as determined by dermal delayed hypersensitivity and solid-phase immunoradiometric tests, respectively. Cross-reactivity in both assays was found against human and bovine cells. Enhancement of atherosclerosis appears to depend not on induction of immune complexes but on specific antibodies and cell-mediated reactions.