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Immunohistochemical localization of different epitopes of advanced glycation end products in human atherosclerotic lesions
- Source :
- Atherosclerosis. 141:61-75
- Publication Year :
- 1998
- Publisher :
- Elsevier BV, 1998.
-
Abstract
- To better understand the role of advanced glycation end products (AGEs) in atherogenesis, we developed specific antibodies against different immunological epitopes of AGE structures, including N e -(carboxymethyl)lysine-protein adduct (CML) and a structure(s) other than CML (nonCML), and demonstrated the immunohistochemical localization of CML- and nonCML-epitopes in atherosclerotic lesions of human aorta, which were obtained at autopsy from 20 nondiabetic patients (12 males and eight females; mean age, 60.8±16.7 years). Monoclonal anti-CML antibody (6D12) recognized not only AGE-modified proteins, but also CML-modified proteins. On the other hand, polyclonal anti-nonCML antibody reacted to AGE-modified proteins, but not to CML-modified proteins. Both antibodies were unreactive to the early-stage products of glycation, including fructose-modified butyloxycarbonyl-lysine and fructose- e -aminocaproic acid. Atherosclerotic lesions included diffuse intimal thickening (DIT), fatty streaks (FS), atherosclerotic plaques (AP) and complicated lesions. An immunohistochemical analysis showed both CML- and nonCML-epitopes to be found along the collagen fibers in DIT in subjects more than 40 years old, but not in subjects less than 40 years old. CML-epitopes accumulated mainly in the cytoplasm of macrophage/foam cells, while nonCML-epitopes accumulated exclusively in the extracellular spaces in FS. APs showed the CML-epitope stored macrophage/foam cells, and the accumulation of both CML- and nonCML-epitopes in the lipid-rich fibrous area. An immunohistochemical analysis with a monoclonal antibody against oxidized low density lipoprotein (FOH1a/DLH3) showed the presence of this antigen within the cytoplasm of the macrophage/foam cells in atherosclerotic lesions, which were also positive for the CML-epitopes. These findings thus suggest that the heterogeneous localization of AGEs in atherosclerotic lesions depends on their different epitopes, and that a close link, therefore, exists between the peroxidation of LDL and the formation of AGEs in atherosclerotic lesions.
- Subjects :
- Adult
Glycation End Products, Advanced
Male
Pathology
medicine.medical_specialty
Arteriosclerosis
medicine.drug_class
Enzyme-Linked Immunosorbent Assay
Monoclonal antibody
Epitope
Epitopes
Antigen
Glycation
hemic and lymphatic diseases
medicine
Humans
Macrophage
Aorta
Aged
biology
Chemistry
Lysine
Macrophages
Antibodies, Monoclonal
Middle Aged
Immunohistochemistry
Extracellular Matrix
Lipoproteins, LDL
Polyclonal antibodies
Immunology
biology.protein
Female
Antibody
Tunica Intima
Cardiology and Cardiovascular Medicine
Subjects
Details
- ISSN :
- 00219150
- Volume :
- 141
- Database :
- OpenAIRE
- Journal :
- Atherosclerosis
- Accession number :
- edsair.doi.dedup.....5262b047d009eae1d2b97478c4e8df72