Oxidized low-density lipoprotein (Ox-LDL) not LDL antiphospholipid syndrome (APS)

J. George, M. Blank, M. Hojnik, E. Bar-Meir, T. Koike, E. Matsuura, M. Lorber, M. Aviram, Y. Shoenfeld

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40 Citations (Scopus)

Abstract

Ox-LDL is thought to play a major role in atherogenesis. The mechanisms mediating the deleterious influences of Ox-LDL include foam cell formation and cell cytotoxicity. The production of anti-Ox-LDL antibodies results in the formation of immune complexes which are taken up at enhanced rate by macrophages, leading to foam cell formation. APS is characterized by repeated venous and arterial thromboembolic phenomena, recurrent fetal loss and thrombocytopenia, associated with the presence of antibodies to negatively charged phospholipids (aPL) (i.e. cardiolipin, phosphatidylserine). Phospholipids bear structural resemblance to LDL, and several studies have indeed proved that aPL display cross-reactivity with anti-Ox-LDL antibodies. In this study we assessed the capacity of oxidized and native forms of LDL to aggravate the clinical picture of experimentally induced APS in naive mice. Mice were actively immunized intradermally with anticardiolipin antibodies and developed a clinical picture resembling APS in humans. Subsequently, the mice were infused with either Ox-LDL, native LDL or PBS, and similar regimens were applied to controls. APS mice infused with Ox-LDL were found to exhibit a significantly more severe form of the disease in comparison with native LDL- and PBS-infused mice, expressed by lower platelet counts (261000/mm3, 535000/mm3 and 455000/mm3, respectively), longer activated partial thromboplastin time (aPTT) (99 ± 12 s, 63 ± 8 s and 74 ± 8 s, respectively) and higher fetal resorption rates (72.7%, 34.4% and 32.6%, respectively). The results of this study show that Ox-LDL, compared with native LDL, aggravates the clinical manifestations of experimental APS and suggest that cross-reactivity of Ox-LDL with phospholipids may provide a pathogenic explanation for this effect.

Original languageEnglish
Pages (from-to)227-233
Number of pages7
JournalClinical and Experimental Immunology
Volume108
Issue number2
DOIs
Publication statusPublished - 1997

Keywords

  • anticardiolipin antibodies
  • antiphospholipid syndrome
  • autoantibodies
  • autoimmunity
  • low-density lipoproteins

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    George, J., Blank, M., Hojnik, M., Bar-Meir, E., Koike, T., Matsuura, E., Lorber, M., Aviram, M., & Shoenfeld, Y. (1997). Oxidized low-density lipoprotein (Ox-LDL) not LDL antiphospholipid syndrome (APS). Clinical and Experimental Immunology, 108(2), 227-233. https://doi.org/10.1046/j.1365-2249.1997.d01-1019.x