1. Effect of combining ACE inhibitor and statin in lupus-prone mice
- Author
-
Koji Kinoshita, Masanori Funauchi, Kazuya Kishimoto, Yasuaki Nagare, Shoichi Hino, Hideki Shimazu, Shinya Ikoma, Masafumi Sugiyama, Yuji Nozaki, and Tomohiro Yano
- Subjects
Mice, Inbred MRL lpr ,Statin ,Combination therapy ,medicine.drug_class ,Immunology ,Lupus nephritis ,Angiotensin-Converting Enzyme Inhibitors ,Blood Pressure ,Imidazolidines ,Kidney ,urologic and male genital diseases ,Nephropathy ,Mice ,Random Allocation ,immune system diseases ,Imidapril ,Animals ,Lupus Erythematosus, Systemic ,Immunology and Allergy ,Medicine ,cardiovascular diseases ,skin and connective tissue diseases ,Pravastatin ,Mice, Inbred C3H ,Systemic lupus erythematosus ,business.industry ,medicine.disease ,Lupus Nephritis ,Specific Pathogen-Free Organisms ,Proteinuria ,Antibodies, Antinuclear ,Immunoglobulin G ,ACE inhibitor ,Cytokines ,Drug Therapy, Combination ,Female ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,business ,medicine.drug - Abstract
MRL-Faslpr mice spontaneously develop a systemic autoimmune disease resembling human systemic lupus erythematosus. The glomerulonephritis in MRL-Faslpr mice is mediated by autoantibodies and autoreactive lymphocytes. To investigate the effect of combination therapy by angiotensin-converting enzyme inhibitor (ACEI) and hydroxymethylglutaryl-coenzyme A reductase inhibitor (statin) for lupus nephritis, we treated MRL-Faslpr mice with imidapril, pravastatin or both agents. Compared with other groups, the mice treated by combination therapy survived longer and showed a significant reduction in proteinuria, renal pathology, including glomerular IgG deposit, and serum anti-DNA Ab. Furthermore, monocyte chemoattractant protein-1 (MCP-1) in the kidney was reduced significantly in the combination therapy group, compared with that in the control group. We conclude that combination therapy with ACEI and statin for MRL-Faslpr mice significantly alleviates autoimmune renal disorder and prolongs survival. These results suggest that combination therapy by ACEI and statin may represent a new approach to the treatment of patients with lupus.
- Published
- 2010
- Full Text
- View/download PDF