Recombinant antibodies to an oxidized low-density lipoprotein epitope induce rapid regression of atherosclerosis in apobec-1(-/-)/low-density lipoprotein receptor(-/-) mice.

Summary, in English

OBJECTIVES: The present study tested the hypothesis that treatment with human recombinant immunoglobulin G1 (IgG1) antibodies against a specific oxidized low-density lipoprotein (oxLDL) epitope will induce regression of existing atherosclerotic lesions in LDL receptor-deficient mice expressing apolipoprotein B-100 (apoB-100) (Apobec-1(-/-)/LDLR(-/-)). BACKGROUND: Oxidized LDL plays an essential role in the pathogenesis of atherosclerosis. We previously showed that an antibody against oxLDL reduces progression of atherosclerosis in mice. METHODS: Apobec-1(-/-)/LDLR(-/-) mice were fed a high-fat diet until they were 24 weeks and were subsequently transferred to chow. Starting at 25 weeks, mice were given 3 weekly injections of either of 2 recombinant human IgG1 antibodies (IEI-E3 or 2D03) against a malondialdehyde-modified apoB-100 peptide sequence. RESULTS: At 25 weeks, atherosclerotic lesions covered 10.3 +/- 3.7% of the descending aorta. Transfer to chow diet resulted in a modest regression of atherosclerosis over a 5-week period (8.28 +/- 4.36%; p = NS). Antibody treatment induced additional regression of atherosclerosis by 50% (2D03; p = 0.001) and 36% (IEI-E3; p = 0.004) compared with control IgG1. The 2D03 treatment also reduced plaque inflammation, enhanced plaque expression of the adenosine triphosphate-binding cassette transporter A1, and inhibited expression of monocyte chemoattractant protein-1 in cultured monocytes. CONCLUSIONS: Human IgG1 against a specific oxLDL epitope can induce rapid and substantial regression of atherosclerotic lesions, possibly by stimulating lipid efflux and inhibiting macrophage recruitment. These recombinant human antibodies could represent a novel strategy for rapid regression/stabilization of atherosclerotic lesions.

• Author: Alexandru Schiopu; Björn Frendéus; Bo Jansson; Ingrid Söderberg; Irena Ljungcrantz; Zufan Araya; Prediman K Shah; Roland Carlsson; Jan Nilsson; Gunilla Nordin Fredrikson
• Department/s: Cardiovascular Research - Immunity and Atherosclerosis
• Publishing year: 2007
• Language: English
• Pages: 2313-2318
• Publication/Series: Journal of the American College of Cardiology
• Volume: 50
• Issue: 24
• Links: http://www.ncbi.nlm.nih.gov/pubmed/18068040?dopt=Abstract; http://dx.doi.org/10.1016/j.jacc.2007.07.081
• Document type: Journal article
• Publisher: Elsevier
• Topic: Cardiac and Cardiovascular Systems
• Keywords: Recombinant Proteins: therapeutic use; Oxidized LDL: physiology; Receptors; Peptide Fragments: immunology; Immunologic Factors: therapeutic use; Immunoglobulin G: therapeutic use; Cytidine Deaminase: physiology; Atherosclerosis: pathology; Atherosclerosis: metabolism; Atherosclerosis: drug therapy; ATP-Binding Cassette Transporters: metabolism; Apolipoprotein B-100: immunology
• Status: Published
• Research group: Cardiovascular Research - Immunity and Atherosclerosis
• ISBN/ISSN/Other: ISSN: 0735-1097