Influence of C3 deficiency on atherosclerosis

• Published in: Circulation (New York, N.Y.) N.Y.), 2002-06, Vol.105 (25), p.3025-3031
• Main Authors: BUONO, Chiara, COME, Carolyn E, WITZTUM, Joseph L, MAGUIRE, Graham F, CONNELLY, Philip W, CARROLL, Michael, LICHTMAN, Andrew H
• Format: Article
• Language: English
• Subjects: Animals; Aorta - pathology; Arteriosclerosis - blood; Arteriosclerosis - immunology; Arteriosclerosis - pathology; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Complement C3 - genetics; Complement C3 - physiology; Immunoglobulins - blood; Lipoproteins - blood; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Phenotype; Receptors, LDL - genetics
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.0000019584.04929.83

The influence of complement activation on atherosclerosis is not well understood. The purpose of this study was to examine the effects of C3 deficiency on the extent and phenotype of atherosclerosis. Aortic atherosclerosis was analyzed in low-density lipoprotein receptor (ldlr)/C3-deficient mice (ldlr(-/-)C3(-/-)) and ldlr(-/-)C3(+/-) littermate control mice after 15 weeks on a 1.25% (wt/wt) cholesterol diet. Serum lipoprotein profiles and immunoglobulin levels were not significantly different between the 2 experimental groups. The lipid-positive en face lesional area in thoracic and abdominal aorta was greater in C3-deficient mice than in control mice (3.9% versus 2.1%, median, P=0.0076). Similarly, the lipid-positive area in aortic arch sections was greater in C3-deficient mice than in controls (0.04 mm2 versus 0.02 mm2, median, P=0.0089). Analysis of aortic arch sections showed greater lesional macrophage content in C3-deficient versus control mice (8.24+/-1.36% versus 5.9+/-1.63% intimal area, mean+/-SEM, P=0.003), less smooth muscle cell content in C3-deficient versus control mice (0.06+/-0.05% versus 0.92+/-0.32% intimal area, mean+/-SEM, P