NDLI: Treatment with apolipoprotein A-1 mimetic peptide reduces lupus-like manifestations in a murine lupus model of accelerated atherosclerosis

Content Provider	Springer Nature : BioMed Central
Author	Woo, Jennifer MP Lin, Zhuofeng Navab, Mohamad Van Dyck, Casey Trejo-Lopez, Yvette Woo, Krystal MT Li, Hongyun Castellani, Lawrence W Wang, Xuping Iikuni, Noriko Rullo, Ornella J Wu, Hui La Cava, Antonio Fogelman, Alan M Lusis, Aldons J Tsao, Betty P
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 (P L, LP < 0.05), lower serum levels of IgG antibodies to double stranded DNA (dsDNA) (P L < 0.05) and oxidized phospholipids (oxPLs) (P L, LP < 0.005), and elevated total and vertebral bone mineral density (P L, LP < 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 (P LP < 0.01), significantly increased mean α-actin stained area (P LP < 0.05), and significantly lower levels of circulating markers for atherosclerosis progression, CCL19 (P L, LP < 0.0005) and VCAM-1 (P L < 0.0002). Conclusions L-4F treatment, alone or with pravastatin, significantly reduced IgG anti-dsDNA and IgG anti-oxPLs, proteinuria, glomerulonephritis, and osteopenia in a murine lupus model of accelerated atherosclerosis. Despite enlarged aortic lesions, increased smooth muscle content, decreased macrophage infiltration, and decreased pro-atherogenic chemokines in L-4F plus pravastatin treated mice suggest protective mechanisms not only on lupus-like disease, but also on potential plaque remodeling in a murine model of systemic lupus erythematosus (SLE) and accelerated atherosclerosis.
Related Links	https://arthritis-research.biomedcentral.com/counter/pdf/10.1186/ar3020.pdf
Ending Page	13
Page Count	13
Starting Page	1
File Format	HTM / HTML
ISSN	14786362
DOI	10.1186/ar3020
Journal	Arthritis Research & Therapy
Issue Number	3
Volume Number	12
Language	English
Publisher	BioMed Central
Publisher Date	2010-05-18
Access Restriction	Open
Subject Keyword	Rheumatology Orthopedics Bone Mineral Density Systemic Lupus Erythematosus Systemic Lupus Erythematosus Patient Pravastatin Femoral Bone Mineral Density
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology Rheumatology
Journal Impact Factor	4.4/2023
5-Year Journal Impact Factor	4.9/2023

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