The Role of Modified Forms of LDL and Corresponding Autoantibodies in the Development of Complications in Diabetes

Chapter
Part of the Contemporary Diabetes book series (CDI)

Abstract

One of the consequences of oxidative stress, which is enhanced in diabetes due to hyperglycemia, is protein modification, which affects LDL. Oxidized LDL (oxLDL), malondialdehyde-modified LDL (MDA-LDL), and advanced glycation end-products LDL (AGE-LDL) are major LDL modifications, which elicit the formation of autoantibodies and immune complexes (IC) in humans, are pro-inflammatory and play a role in the pathogenesis of atherosclerosis. The proinflammatory potential of modified LDL (mLDL) is enhanced several fold when mLDL combines with specific IgG antibodies. Clinical studies by our group have shown that the levels of mLDL in circulating IC significantly predict the development of diabetic complications. Furthermore, the composition of mLDL in IC modulates the pattern of cell activation. In the case of macrovascular disease, when the predominant modifications in IC are oxLDL and AGE LDL there is a strong association with intima-media thickening, but not with acute events. In contrast, high levels of MDA-LDL in IC are associated with acute CVD events. In vitro studies suggest that the reason for these differences result from different effects of mLDL-IC in macrophages and other cells.

Keywords

Cholesterol Permeability Foam Creatinine Glutathione 

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© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of MedicineMedical University of South CarolinaCharlestonUSA
  2. 2.Ralph A. Johnson VA Medical CenterCharlestonUSA
  3. 3.Department of Microbiology and ImmunologyMedical University of South CarolinaCharlestonUSA

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