Treatment with apolipoprotein A-1 mimetic peptide reduces lupus-like manifestations in a murine lupus model of accelerated atherosclerosis 英文参考文献.docVIP

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Treatment with apolipoprotein A-1 mimetic peptide reduces lupus-like manifestations in a murine lupus model of accelerated atherosclerosis 英文参考文献.doc

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Treatment with apolipoprotein A-1 mimetic peptide reduces lupus-like manifestations in a murine lupus model of accelerated atherosclerosis 英文参考文献

Woo et al. Arthritis Research Therapy 2010, 12:R93 /content/12/3/R93 RESEARCH ARTICLE Open Access Treatment with apolipoprotein A-1 mimetic Research article peptide reduces lupus-like manifestations in a murine lupus model of accelerated atherosclerosis Jennifer MP Woo1, Zhuofeng Lin1, Mohamad Navab2, Casey Van Dyck1, Yvette Trejo-Lopez1, Krystal MT Woo1, Hongyun Li1, Lawrence W Castellani3, Xuping Wang3, Noriko Iikuni1, Ornella J Rullo4, Hui Wu1, Antonio La Cava1, Alan M Fogelman5, Aldons J Lusis2 and Betty P Tsao*1 Abstract Introduction: The purpose of this study was to evaluate the effects of L-4F, an apolipoprotein A-1 mimetic peptide, alone or with pravastatin, in apoE-/-Fas-/-C57BL/6 mice that spontaneously develop immunoglobulin G (IgG) autoantibodies, glomerulonephritis, osteopenia, and atherosclerotic lesions on a normal chow diet. Methods: Female mice, starting at eight to nine weeks of age, were treated for 27 weeks with 1) pravastatin, 2) L-4F, 3) L-4F plus pravastatin, or 4) vehicle control, followed by disease phenotype assessment. Results: In preliminary studies, dysfunctional, proinflammatory high-density lipoproteins (piHDL) were decreased six hours after a single L-4F, but not scrambled L-4F, injection in eight- to nine-week old mice. After 35 weeks, L-4F-treated mice, in the absence/presence of pravastatin, had significantly smaller lymph nodes and glomerular tufts (PL, LP lower serum levels of IgG antibodies to double stranded DNA (dsDNA) (PL 0.05) and oxidized phospholipids (oxPLs) (PL, LP 0.005), and elevated total and vertebral bone mineral density (PL, LP 0.05), 0.01) compared to vehicle controls. Although all treatment groups presented larger aortic root lesions compared to vehicle controls, enlarged atheromas in combination treatment mice had significantly less infiltrated CD68+ macrophages (PLP 0.01), significantly increased mean α-actin stained area (PLP 0.05), and significantly lower levels of circulating mark