Oxidation-specific epitopes as targets for biotheranostic applications in humans: biomarkers, molecular imaging and therapeutics

Curr Opin Lipidol. 2013 Oct;24(5):426-37. doi: 10.1097/MOL.0b013e328364e85a.

Abstract

Purpose of review: Emerging data demonstrate the potential of translational applications of antibodies directed against oxidation-specific epitopes (OSEs). 'Biotheranostics' as used in this context in cardiovascular disease (CVD) describes targeting of OSEs for biomarker, therapeutic and molecular imaging diagnostic applications.

Recent findings: Atherogenesis can be viewed as a chronic, maladaptive inflammatory response to OSE and related antigens. Lipid oxidation collectively yields a large variety of OSE, such as oxidized phospholipids (OxPL) and malondialdehyde epitopes. OSEs are immunogenic, proinflammatory, proatherogenic and plaque destabilizing and represent danger-associated molecular patterns (DAMPs). DAMPs are recognized by the innate immune system via pattern recognition receptors, including scavenger receptors, IgM natural antibodies and complement factor H, which bind, neutralize and/or facilitate their clearance. Biomarker assays measuring OxPL present on apolipoprotein B-100 lipoproteins, and particularly on lipoprotein (a), predict the development of CVD events. In contrast, OxPL on plasminogen facilitate fibrinolysis and may reduce atherothrombosis. Oxidation-specific antibodies attached to magnetic nanoparticles image lipid-rich, oxidation-rich plaques. Infusion or overexpression of oxidation-specific antibodies reduces the progression of atherosclerosis by potentially neutralizing and clearing OSE and preventing foam cell formation, suggesting similar applications in humans.

Summary: Using the accelerating knowledge base and improved understanding of the interplay of oxidation, inflammation and innate and adaptive immunity in atherogenesis, emerging clinical applications of oxidation-specific antibodies may identify, monitor and treat CVD in humans.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Antibodies / chemistry
  • Antibodies / immunology
  • Antibodies / pharmacology
  • Atherosclerosis* / blood
  • Atherosclerosis* / immunology
  • Atherosclerosis* / pathology
  • Atherosclerosis* / therapy
  • Biomarkers / blood
  • Blood Proteins / immunology
  • Blood Proteins / metabolism
  • Epitopes
  • Foam Cells / immunology
  • Foam Cells / metabolism
  • Foam Cells / pathology
  • Humans
  • Inflammation / blood
  • Inflammation / immunology
  • Inflammation / pathology
  • Inflammation Mediators / blood*
  • Inflammation Mediators / immunology
  • Magnetite Nanoparticles / chemistry
  • Molecular Imaging / methods*
  • Oxidation-Reduction
  • Plaque, Atherosclerotic* / blood
  • Plaque, Atherosclerotic* / immunology
  • Plaque, Atherosclerotic* / pathology
  • Plaque, Atherosclerotic* / therapy

Substances

  • Antibodies
  • Biomarkers
  • Blood Proteins
  • Epitopes
  • Inflammation Mediators
  • Magnetite Nanoparticles