Document Detail


Oxidation-specific epitopes as targets for biotheranostic applications in humans: biomarkers, molecular imaging and therapeutics.
MedLine Citation:
PMID:  23995232     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Yury I Miller; Sotirios Tsimikas
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  Current opinion in lipidology     Volume:  24     ISSN:  1473-6535     ISO Abbreviation:  Curr. Opin. Lipidol.     Publication Date:  2013 Oct 
Date Detail:
Created Date:  2013-09-06     Completed Date:  2014-03-25     Revised Date:  2014-07-11    
Medline Journal Info:
Nlm Unique ID:  9010000     Medline TA:  Curr Opin Lipidol     Country:  England    
Other Details:
Languages:  eng     Pagination:  426-37     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Antibodies / chemistry,  immunology,  pharmacology
Atherosclerosis* / blood,  immunology,  pathology,  therapy
Biological Markers / blood
Blood Proteins / immunology,  metabolism
Epitopes
Foam Cells / immunology,  metabolism,  pathology
Humans
Inflammation / blood,  immunology,  pathology
Inflammation Mediators / blood*,  immunology
Magnetite Nanoparticles / chemistry
Molecular Imaging / methods*
Oxidation-Reduction
Plaque, Atherosclerotic* / blood,  immunology,  pathology,  therapy
Grant Support
ID/Acronym/Agency:
HL055798/HL/NHLBI NIH HHS; HL088093/HL/NHLBI NIH HHS; HL093767/HL/NHLBI NIH HHS; P01 HL055798/HL/NHLBI NIH HHS; P01 HL088093/HL/NHLBI NIH HHS; R01 HL093767/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies; 0/Biological Markers; 0/Blood Proteins; 0/Epitopes; 0/Inflammation Mediators; 0/Magnetite Nanoparticles
Comments/Corrections

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