Reduction of atherosclerosis in low-density lipoprotein receptor-deficient mice by passive administration of antiphospholipid antibody.
OBJECTIVE
Patients with antiphospholipid syndrome (APS) are at a high risk of developing atherosclerotic complications. Conversely, individuals with primary atherosclerosis have an increased prevalence of antiphospholipid antibodies (aPL) and antibodies to oxidized low-density lipoproteins (ox-LDL). Several studies suggest that these two antibody populations may in fact overlap, although it is unclear how aPL contribute to pathogenesis. In this study, we characterized an IgG monoclonal aPL and assessed its ability to modulate atherosclerosis in low-density lipoprotein receptor-deficient (LDLR(-/-)) mice.


METHODS
The cardiolipin-reactive monoclonal antibody FB1 was obtained from an (NZW x BXSB)F(1) mouse, a strain with APS features that make it prone to fatal myocardial infarctions. Using an enzyme-linked immunosorbent assay, we investigated the binding of this antibody to phospholipid and LDL antigens. We also passively administered FB1 to atherosclerosis-prone mice to determine its effect on atherogenesis.


RESULTS
In contrast to earlier studies of aPL that were specific for oxidized forms of LDL, FB1 cross-reacted with both native LDL and ox-LDL. In vivo, passive administration of FB1 significantly reduced plaque formation in atherosclerosis-prone LDLR(-/-) mice.


CONCLUSIONS
These results indicate that some aPL may play a protective role in atherogenesis and suggest a novel approach to the prevention of atherosclerosis.
Nicolo
Danielle
D
Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
Goldman
Bruce I
BI
Monestier
Marc
M
D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001161:Arteriosclerosis / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D010084:Oxidation-Reduction; D011485:Protein Binding / Q000276:immunology; D011973:Receptors, LDL / Q000235:genetics*
D017152:Antibodies, Antiphospholipid; D000911:Antibodies, Monoclonal; D011973:Receptors, LDL