Autoimmune responses against the apo B-100 LDL receptor-binding site protect against arterial accumulation of lipids in LDL receptor deficient mice.

Summary, in English

Background: Oxidation of LDL is associated with generation of autoantibodies against a large number of different aldehyde-modified peptide sequences in apo B-100. Autoantibodies recognizing peptide sequences in the LDL receptor-binding region of apo B-100 could potentially affect both cholesterol metabolism and atherosclerosis. The aim of the present study was to determine physiological effects of induction of immune responses against the apo B-100 LDL receptor-binding site in mice deficient for the LDL receptor. Methods and results: Mice received three immunizations, beginning at 6 weeks of age, with aldehyde-modified or nonmodified peptides corresponding to the amino acid sequence of the LDL receptor-binding site. Analysis of antibody response by ELISA unexpectedly revealed high titers of pre-existing IgG against both native and aldehyde-modified binding site sequences in non-immunized mice. Immunization with aldehyde-modified binding site sequences resulted in an almost complete down-regulation of this autoimmune response. It was also associated with a rapid increase in lipid-rich plaques in the aorta and a substantial depletion of the lipid content of the liver, whereas plasma lipid and apo B values were similar in all groups. Conclusions: These observations demonstrate existence of an endogenous T cell-dependent autoimmune response against the LDL receptor-binding site in LDL receptor(-/-) mice and suggest that this may help to prevent accumulation of lipoprotein lipids in the artery wall, whereas immunization with the corresponding aldehyde modified sequence down-regulates this response and induces substantial atherosclerotic development.

• Författare: Gunilla Nordin Fredrikson; Marie Lindholm; Irena Ljungcrantz; Ingrid Söderberg; Prediman K Shah; Jan Nilsson
• Avdelning/ar: Kardiovaskulär forskning - immunitet och ateroskleros
• Publiceringsår: 2007
• Språk: Engelska
• Sidor: 122-130
• Publikation/Tidskrift/Serie: Autoimmunity
• Volym: 40
• Issue: 2
• Länkar: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17453711&dopt=Abstract; http://dx.doi.org/10.1080/08916930601165107
• Dokumenttyp: Artikel i tidskrift
• Förlag: Taylor & Francis
• Ämne: Rheumatology and Autoimmunity
• Nyckelord: apolipoprotein; autoantibodies; LDL-receptor; binding-site; atherosclerosis
• Status: Published
• Forskningsgrupp: Cardiovascular Research - Immunity and Atherosclerosis
• ISBN/ISSN/Övrigt: ISSN: 0891-6934