Inhibition of injury-induced arterial remodelling and carotid atherosclerosis by recombinant human antibodies against aldehyde-modified apoB-100.
OBJECTIVE
The immune system plays an important regulatory role in the development of atherosclerotic plaques and neointima formation following various types of angioplasty. In the present study we investigated the effect of antibodies against aldehyde-modified apolipoprotein B-100 (apoB-100), a component of oxidized LDL, on atherosclerosis and response to arterial injury in mice.


METHODS
The ability of a high affinity human recombinant antibody (2D03), specific for malondialdehyde-modified apoB-100, to influence formation of atherosclerosis as well as remodelling and neointima formation after a collar-induced injury of the carotid artery was studied in LDL receptor(-/-) mice over-expressing human apoB-100.


RESULTS
The antibody recognized epitopes present in mouse plasma and reduced the plasma level of oxidized LDL by 34%. Antibody treatment inhibited injury-induced restrictive vascular remodelling but did not influence the size of the neointima. Atherosclerosis in the uninjured contra lateral carotid artery was determined by computerized image analysis and the mean plaque area in animals given control IgG1 was 7608+/-10,336 micro m(2). In contrast, essentially no plaques were present in animals treated with the 2D03 antibody (397+/-235 micro m(2), P<0.01 versus control IgG1).


CONCLUSIONS
Treatment with antibodies against aldehyde-modified apoB-100 dramatically reduces atherosclerosis and inhibits restrictive vascular remodelling in mice expressing human apoB-100.
Ström
Asa
A
Department of Experimental Medical Science, Lund University, BMC, C12, SE-22184 Lund, Sweden. asa.strom@med.lu.se
Fredrikson
Gunilla Nordin
GN
Schiopu
Alexandru
A
Ljungcrantz
Irena
I
Söderberg
Ingrid
I
Jansson
Bo
B
Carlsson
Roland
R
Hultgårdh-Nilsson
Anna
A
Nilsson
Jan
J