P119	IgG1 antibodies against oxLDL epitopes induce regression of advanced atherosclerotic plaques in LDLR-/- APOBEC mice.
1A.Schiopu, 2B.Jansson, 3P.K.Shah, 3R.Carlsson, 1J.Nilsson, 1G.Nordin Fredrikson
1Department of Medicine, Malmö University Hospital, Lund University, Malmö, SE; 2BioInvent International AB, Lund, SE; 3Atherosclerosis Research Center, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, US.

Objective: The purpose of our study was to assess the effects of recombinant human IgG1 antibodies against specific oxLDL epitopes on advanced atherosclerotic lesions in mice. Methods: We have tested 2 recombinant human IgG1 antibodies directed to malondialdehyde (MDA)-modified ApoB-100 peptide sequences. Three weekly 1 mg antibody doses were injected intraperitoneally starting at 25 weeks in LDLR-/- Apobec mice, which were then sacrificed at 29 weeks of age. IgG1 antibodies directed against fluorescein isothiocyanate, which do not bind to either native or oxidised LDL, and a baseline group sacrificed at 25 weeks of age, to asses plaque status before immunization, were used as controls. Results: Both antibodies induced a significant regression of already present atherosclerotic plaques in the descending aorta as compared to baseline. This effect was not present in the isotype control group. The changes did not depend on alterations in weight, cholesterol or triacylglycerol content in mice plasma. Conclusions: The present study suggests that antibody treatment has the ability to reduce the extent of already present, advanced atherosclerotic lesions. Passive immunization with antibodies directed against oxLDL epitopes might constitute a future fast acting therapy for patients at high risk for acute cardiovascular events.

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