Identification of the target for therapeutic recombinant anti-apoB-100 peptide antibodies in human atherosclerotic lesions

Atherosclerosis
Isabel GonçalvesJan Nilsson

Abstract

Accumulation of oxidized LDL in the arterial wall is believed to play a key role in the development of atherosclerosis. Experimental studies have identified the presence of immune responses against epitopes in oxidized LDL that protects against atherosclerosis. We have produced human recombinant IgG against one of these epitopes (aldehyde-modified apoB-100 amino acids 661-680) and demonstrated that treatment with this human IgG1 2D03 antibody markedly reduces atherosclerosis in hypercholesterolemic mice. In the present study, we screened a panel of 25 carotid plaques associated with clinical symptoms and 26 clinically silent plaques obtained at surgery for presence of the aldehyde-modified apoB-100 peptide defined by the 2D03 antibody and compared the expression of this epitope with other plaque constituents, plasma lipoproteins levels, plasma oxidized LDL and autoantibodies against apoB-100 peptides. We demonstrated that the epitope is commonly expressed in human atherosclerotic plaques and that plaques associated with clinical symptoms have an almost three-fold higher content of this epitope (8.6+/-4.9% versus 22.1+/-12.2% immunostaining of total plaque area, p<0.0005). There was also a significant association between 2D03 ep...Continue Reading

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Citations

Jan 25, 2013·Immunologic Research·Chrysoulla PieridesErnesto Oviedo-Orta
Oct 21, 2011·Thrombosis and Haemostasis·S C A de Jager, J Kuiper
Feb 7, 2018·Cerebrovascular Diseases Extra·Sanela HalakGiuseppe Asciutto
Feb 27, 2016·Arteriosclerosis, Thrombosis, and Vascular Biology·Harry BjörkbackaGunilla Nordin Fredrikson
Nov 1, 2015·Clinical Science·Hyo Joon KimBert Binas
Apr 24, 2020·Circulation Research·Jan Nilsson, Göran K Hansson
Apr 29, 2021·Scientific Reports·Pontus DunérEva Bengtsson
Jun 3, 2021·International Journal of Molecular Sciences·Eunhye Ji, Sahmin Lee

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