The HMG-CoA reductase inhibitor rosuvastatin promotes complement factor H expression in apolipoprotein E-knockout mice

The aim of this study was to investigate the relationship between plaque severity and the expression of complement factor H (CFH) in an apo E-knockout mouse model of atherosclerosis. An additional objective was to determine the effect of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) on this relationship. Eight-week-old apo E-knockout mice were divided randomly into 2 groups: group A (atherosclerotic model group, n=14), and group B (rosuvastatin-treated group, n=8). Ten age-and genetic background-matched healthy C57BL/6 mice were used as a control group. After 20 weeks of continuous intragastric rosuvastatin administration, aorta samples were taken for H&E and immunohistochemical staining. Quantitative real-time PCR was performed to determine the level of CFH transcription, and western blot analysis was performed to measure CFH protein expression. Immunohistochemical staining showed that CFH was expressed in group A, and this was accompanied by increased mRNA and protein levels and the severity of atherosclerosis. However, none of these changes were observed in the control group. Rosuvastatin upregulated CFH mRNA expression and increased CFH protein levels. The plasma level of cholesterol was higher in group A than that in the control group (P<0.05). Furthermore, serum high-sensitive C-reactive protein and C3a levels decreased significantly in group B compared with those in group A (P<0.05). This study verified expression of CFH in atherosclerotic plaques in apo E-knockout mice and shows that rosuvastatin attenuated lesions and stabilized aortic plaques, possibly by increasing the expression of CFH and suppressing inflammation.