Differential expression of oxidation-specific epitopes and apolipoprotein(a) in progressing and ruptured human coronary and carotid atherosclerotic lesions
The relationships between oxidation-specific epitopes (OSE) and lipoprotein (a) [Lp(a)] and progressive atherosclerosis and plaque rupture have not been determined. Coronary artery sections from sudden death victims and carotid endarterectomy specimens were immunostained for apoB-100, oxidized phosp...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2012-12-01
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| Series: | Journal of Lipid Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520418127 |
| _version_ | 1818920501039333376 |
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| author | Rogier A. van Dijk Frank Kolodgie Amir Ravandi Gregor Leibundgut Patrick P. Hu Anand Prasad Ehtisham Mahmud Edward Dennis Linda K. Curtiss Joseph L. Witztum Bruce A. Wasserman Fumiyuki Otsuka Renu Virmani Sotirios Tsimikas |
| author_facet | Rogier A. van Dijk Frank Kolodgie Amir Ravandi Gregor Leibundgut Patrick P. Hu Anand Prasad Ehtisham Mahmud Edward Dennis Linda K. Curtiss Joseph L. Witztum Bruce A. Wasserman Fumiyuki Otsuka Renu Virmani Sotirios Tsimikas |
| author_sort | Rogier A. van Dijk |
| collection | DOAJ |
| description | The relationships between oxidation-specific epitopes (OSE) and lipoprotein (a) [Lp(a)] and progressive atherosclerosis and plaque rupture have not been determined. Coronary artery sections from sudden death victims and carotid endarterectomy specimens were immunostained for apoB-100, oxidized phospholipids (OxPL), apo(a), malondialdehyde-lysine (MDA), and MDA-related epitopes detected by antibody IK17 and macrophage markers. The presence of OxPL captured in carotid and saphenous vein graft distal protection devices was determined with LC-MS/MS. In coronary arteries, OSE and apo(a) were absent in normal coronary arteries and minimally present in early lesions. As lesions progressed, apoB and MDA epitopes did not increase, whereas macrophage, apo(a), OxPL, and IK17 epitopes increased proportionally, but they differed according to plaque type and plaque components. Apo(a) epitopes were present throughout early and late lesions, especially in macrophages and the necrotic core. IK17 and OxPL epitopes were strongest in late lesions in macrophage-rich areas, lipid pools, and the necrotic core, and they were most specifically associated with unstable and ruptured plaques. Specific OxPL were present in distal protection devices. Human atherosclerotic lesions manifest a differential expression of OSEs and apo(a) as they progress, rupture, and become clinically symptomatic. These findings provide a rationale for targeting OSE for biotheranostic applications in humans. |
| first_indexed | 2024-12-20T01:22:45Z |
| format | Article |
| id | doaj.art-e290b51a9e7e4581bcc078451e21baa7 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-20T01:22:45Z |
| publishDate | 2012-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-e290b51a9e7e4581bcc078451e21baa72022-12-21T19:58:23ZengElsevierJournal of Lipid Research0022-22752012-12-01531227732790Differential expression of oxidation-specific epitopes and apolipoprotein(a) in progressing and ruptured human coronary and carotid atherosclerotic lesionsRogier A. van Dijk0Frank Kolodgie1Amir Ravandi2Gregor Leibundgut3Patrick P. Hu4Anand Prasad5Ehtisham Mahmud6Edward Dennis7Linda K. Curtiss8Joseph L. Witztum9Bruce A. Wasserman10Fumiyuki Otsuka11Renu Virmani12Sotirios Tsimikas13CVPath Institute, Gaithersburg, MDCVPath Institute, Gaithersburg, MDDepartments of Medicine, University of California at San Diego, La Jolla, CADepartments of Medicine, University of California at San Diego, La Jolla, CADepartments of Medicine, University of California at San Diego, La Jolla, CADepartments of Medicine, University of California at San Diego, La Jolla, CADepartments of Medicine, University of California at San Diego, La Jolla, CAPharmacology, and University of California at San Diego, La Jolla, CA; Chemistry and Biochemistry, University of California at San Diego, La Jolla, CAScripps Research Institute, La Jolla, CA; andDepartments of Medicine, University of California at San Diego, La Jolla, CARussell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins Hospital, Baltimore, MDCVPath Institute, Gaithersburg, MDCVPath Institute, Gaithersburg, MDTo whom correspondence should be addressed. e-mail: stsimikas@ucsd.edu.; Departments of Medicine, University of California at San Diego, La Jolla, CA; To whom correspondence should be addressed. e-mail: stsimikas@ucsd.edu.The relationships between oxidation-specific epitopes (OSE) and lipoprotein (a) [Lp(a)] and progressive atherosclerosis and plaque rupture have not been determined. Coronary artery sections from sudden death victims and carotid endarterectomy specimens were immunostained for apoB-100, oxidized phospholipids (OxPL), apo(a), malondialdehyde-lysine (MDA), and MDA-related epitopes detected by antibody IK17 and macrophage markers. The presence of OxPL captured in carotid and saphenous vein graft distal protection devices was determined with LC-MS/MS. In coronary arteries, OSE and apo(a) were absent in normal coronary arteries and minimally present in early lesions. As lesions progressed, apoB and MDA epitopes did not increase, whereas macrophage, apo(a), OxPL, and IK17 epitopes increased proportionally, but they differed according to plaque type and plaque components. Apo(a) epitopes were present throughout early and late lesions, especially in macrophages and the necrotic core. IK17 and OxPL epitopes were strongest in late lesions in macrophage-rich areas, lipid pools, and the necrotic core, and they were most specifically associated with unstable and ruptured plaques. Specific OxPL were present in distal protection devices. Human atherosclerotic lesions manifest a differential expression of OSEs and apo(a) as they progress, rupture, and become clinically symptomatic. These findings provide a rationale for targeting OSE for biotheranostic applications in humans.http://www.sciencedirect.com/science/article/pii/S0022227520418127 |
| spellingShingle | Rogier A. van Dijk Frank Kolodgie Amir Ravandi Gregor Leibundgut Patrick P. Hu Anand Prasad Ehtisham Mahmud Edward Dennis Linda K. Curtiss Joseph L. Witztum Bruce A. Wasserman Fumiyuki Otsuka Renu Virmani Sotirios Tsimikas Differential expression of oxidation-specific epitopes and apolipoprotein(a) in progressing and ruptured human coronary and carotid atherosclerotic lesions Journal of Lipid Research |
| title | Differential expression of oxidation-specific epitopes and apolipoprotein(a) in progressing and ruptured human coronary and carotid atherosclerotic lesions |
| title_full | Differential expression of oxidation-specific epitopes and apolipoprotein(a) in progressing and ruptured human coronary and carotid atherosclerotic lesions |
| title_fullStr | Differential expression of oxidation-specific epitopes and apolipoprotein(a) in progressing and ruptured human coronary and carotid atherosclerotic lesions |
| title_full_unstemmed | Differential expression of oxidation-specific epitopes and apolipoprotein(a) in progressing and ruptured human coronary and carotid atherosclerotic lesions |
| title_short | Differential expression of oxidation-specific epitopes and apolipoprotein(a) in progressing and ruptured human coronary and carotid atherosclerotic lesions |
| title_sort | differential expression of oxidation specific epitopes and apolipoprotein a in progressing and ruptured human coronary and carotid atherosclerotic lesions |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520418127 |
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