Development of anti-chloro (192) tyrosine HDL apoA-I antibodies for the immunodiagnosis of cardiovascular diseases
| Autor: | Gilles Joucla, Marie-Josée Jacobin-Valat, Xavier Santarelli, Krishnan Venkataraman, Rajasekar R. Prasanna, Mookambeswaran A. Vijayalakshmi, N. S. Jayaprakash, Kirubanandhan Lokeshwaran, Wilfrid Dieryck, Audrey Hemadou, Gisèle Clofent-Sanchez |
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| Přispěvatelé: | Centre de résonance magnétique des systèmes biologiques (CRMSB), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Biotechnologie des protéines recombinantes à visée santé, Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
[SDV.BIO]Life Sciences [q-bio]/Biotechnology Apolipoprotein B medicine.drug_class [SDV]Life Sciences [q-bio] Immunology Monoclonal antibody 03 medical and health sciences 0302 clinical medicine In vivo polycyclic compounds medicine Immunology and Allergy Tyrosine ComputingMilieux_MISCELLANEOUS biology Chemistry Reverse cholesterol transport nutritional and metabolic diseases 3. Good health 030104 developmental biology Biochemistry Myeloperoxidase biology.protein lipids (amino acids peptides and proteins) Antibody Keyhole limpet hemocyanin 030215 immunology |
| Zdroj: | Journal of Immunological Methods Journal of Immunological Methods, Elsevier, 2019, 474, pp.112637. ⟨10.1016/j.jim.2019.112637⟩ |
| ISSN: | 0022-1759 |
| Popis: | High density lipoproteins (HDL) are considered cardio protective. Apolipoprotein A-I (apoA-I), a major component of HDL helps in reverse cholesterol transport, whose function is greatly affected during atherosclerosis due to oxidation by myeloperoxidase. Amino acid tyrosine residue of apoA-I at position 192 and 166 are sensitive to oxidation by myeloperoxidase resulting in the generation of chlorinated and nitrated apoA-I and they are believed to be present in atherosclerotic plaques and in circulation. These oxidized apoA-I have been suggested as potential indicator(s) of CVD risks in humans. To detect the levels of oxidized apoA-I there is a need for developing monoclonal antibodies (mAbs) with high specificity and sensitivity that could be utilized routinely in clinical immune based assays for blood plasma or for in vivo imaging. In this study, chemically chlorinated apoA-I (chlorinated 192tyrosine- apoA-I) and a short synthetic peptide, containing the corresponding chlorinated tyrosine residue, conjugated to keyhole limpet hemocyanin (KLH) carrier protein were used for immunization. Stable hybridoma clones F7D5 and G11E3 were found to be highly sensitive and reactive towards chlorinated 192tyrosine- apoA-I. Interestingly, these mAbs also displayed positive reaction with atherosclerotic plaques obtained from mouse and human biopsies. In vitro or in vivo diagnostic tests could be developed either by detecting oxidized apoA-I in human plasma or by directly imaging atheroma plaques as both mAbs were shown to stain human atheroma. The anti-chlorinated 192tyrosine- apoA-I mAbs described in this study may have a high diagnostic potential in predicting CVD risks. |
| Databáze: | OpenAIRE |
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